In an affluent Baltimore suburb, all hell is about to break loose in the home of the Gravels. Bosley Gravel (George Stover) has a discussion on the front porch with Dr. Evans (Al Strapelli). Gravel has had his wife Peggy (Mink Stole) released from a mental institution; Evans feels she should have stayed for a while longer, but Gravel says that Peggy's breakdown is "part of the past now". However, inside the house, Peggy is in hysterics. Her young son and his friends are playing baseball in the front yard, and one of them accidentally hits a baseball through Peggy's window. She immediately starts shrieking and views the accident as an assassination attempt. She begins screaming at the children, then is driven even further insane when the phone rings and it's a wrong number. She viciously berates the caller and goes downstairs. Grizelda Brown (Jean Hill) is a very large black woman who works as a maid for the Gravels; she is doing housework when Peggy appears in her frantic state. Grizelda assures her that everything is alright and she's just upset, but Peggy tells her that someone just tried to kill her.Peggy goes off looking for her two youngest children and finds them naked, playing an innocent game of doctor; horrified, she screams at them and calls them "sodomites", ranting that her daughter Beth (who appears to be about 8 years old) could be pregnant. Meanwhile, Bosley finds Grizelda drinking from his liquor cabinet, and they argue about it. Grizelda is defiant, but Bosley finds his savings account book, his lottery ticket, and two rolls of toilet paper in Grizelda's purse. Before he can call the police, Peggy appears and confronts Bosley in a deranged way, ranting about her paranoid delusions before disappearing upstairs. Bosley goes upstairs to administer an injection for Peggy, and leaves Grizelda alone in the kitchen.Upstairs, Peggy refuses the injection and reacts with hostility to Bosley, who says "Peggy, I might have to commit you again!" In response, Peggy smashes glass over his head and screams for Grizelda, who rushes upstairs. Grizelda, who appears to weigh well over 300 pounds, sits on Bosley and kills him. Horrified, the two of them run from the house and leave in Peggy's car.In the car they have an argument; Grizelda announces that they are going to sleep in the woods overnight to hide out from the police, and Peggy takes a haughty attitude with her. As a result, Grizelda forces the car to a halt and drags Peggy from the driver's seat outside the car. "I ain't your maid anymore, bitch, I'm your sister in crime!" she tells her, and Peggy seems to suddenly fear for her life. Before the altercation can go any further, a very strange looking policeman (Turkey Joe) pulls up on a motorcycle. The cop immediately knows who Peggy and Grizelda are, saying that the authorities have already learned of the murder they committed and are looking for them this very minute. Instead of arresting them, the policeman assaults them, removing his uniform to reveal women's lingerie underneath. He forces the women to remove their panties, which he then puts on, and kisses them lewdly (something that is made even more disgusting by the fact that the policeman's gums are constantly bleeding). The cop makes a brief reference to a place called Mortville; Peggy and Grizelda have never heard of it, but he tells them that it is a place where killers can live scot free. In exchange for their cooperation, he lets them escape to Mortville, and they run off through the woods for their destination.When they find Mortville, they realize it is a ramshackle village built entirely out of garbage. The place is populated by bizarre, degenerate characters. Grizelda accepts it for what it is, but Peggy remains haughty. The two of them find a house that offers a "room for rent", and they are greeted by an extremely abrasive woman named Mole McHenry (Susan Lowe). Peggy tries to ingratiate herself to Mole, who immediately sees through her, but Grizelda makes a decent impression and Mole offers to rent them a room, stealing Grizelda's purse as payment. Inside she finds six dollars cash, which Mole considers a large amount of money, and the lottery ticket Grizelda stole from Bosley. Mole takes this as well, announcing "I'll take this, and I'LL win it." Then she invites Grizelda and Peggy to dinner, telling Grizelda "You look like you got a big appetite!"Inside Mole's house, they meet Mole's girlfriend, Muffy St. Jacques (Liz Renay). Muffy is a sexpot type, and Mole derides her for being "lazy" by sleeping late; she also jealously accuses her of having sexual dreams about men. When Muffy makes a flippant comment in response, Mole violently impales her hand with a large fork. When Grizelda and Peggy see that the "dinner" Mole has prepared is a dead dog, they try and back out of eating, but the borderline violent Mole tries to force them to eat it.Before they can, strange looking goons who wear costumes that resemble S&M bondage gear break into the house and kidnap Peggy and Grizelda, ushering them into the back of a truck and driving off with them. Before they leave, Mole tries to console them "Don't worry, it's standard procedure in Mortville!" In the back of the truck, Grizelda tries to kiss Peggy romantically; the icy Peggy reacts with shock and disgust. They are taken to a castle on the border of Mortville, where they are brought before Mortville's facist dictator, Queen Carlotta (Edith Massey). Carlotta is carried around by her goons, as she seems too large to walk on her own. She intimidates the women, telling them that she knows they are on the lam for murder and that she expects them to live in a constant state of "mortification" in Mortville. The goons force them to eat live roaches and Carlotta makes them watch the execution of a prisoner, whose only crime seems to be defying the Queen. She sends them off to see the "ugly experts", where they will get a humiliating makeover. When they've gone, Carlotta drops her theatrical attitude and has one of her goons sexually stimulate her by stripping and dancing nude. Carlotta then has her goons take her to see her daughter, Princess Coo-Coo (Mary Vivian Pearce). It seems Coo-Coo has been acting defiant, sneaking out of the castle to rendezvous with her lover Herbert, one of Mortville's garbage men. Carlotta scolds Coo-Coo and tells her that she disapproves of her relationship with Herbert. As punishment, Carlotta grounds Coo-Coo to her room for several years. Unbeknownst to Coo-Coo, Carlotta orders her goons to assassinate Herbert on sight.Back at Mole's, Peggy and Grizelda return wearing outrageous clothing and makeup. Mole and Muffy laugh at them, and Peggy tries to insult Mole, causing her to threaten Peggy physically. Muffy tells a story about how she ended up in Mortville, and we see a flashback to the night Muffy's life went wrong. Muffy and her former husband are seen arriving home after a party to find that their teenage babysitter is having a wild party in their home. Drugs and alcohol are rampant, and Muffy's husband (Roland Hertz) chases all of the kids out of the house. Muffy finds the babysitter upstairs in their bed naked with a boy; when she demands to know where her baby Freddy is, the babysitter (Pirie Woods) tells her that she thinks she left him in the kitchen. Muffy finds the baby boy inside the closed refrigerator and goes berserk, whacking the babysitter on the head with a frying pan and shoving her face in a large bowl of dog food, suffocating her. When Muffy's husband sees what happened, she runs away and takes off in their car; the husband tries to stop her, but Muffy rolls up the window on his neck, choking him to death and dragging his body along as she drives off. Mole tells her own story immediately after, revealing that she was a female wrestler who went berserk at a match and murdered her male opponent.After the stories, Mole reveals that she is betting on the lottery ticket she took from Peggy and Grizelda to bring them some much-needed cash to get them out of their hopeless situation. Peggy is indignant, shrieking that the lottery ticket belongs to her; she further enrages Mole by saying "We need money, we're not trash like you!" Grizelda defuses the situation by taking Peggy back to their 'room', which is a small shed behind the house with a bed in it. Both couples then have sex, although Peggy does so begrudgingly, performing oral sex on Grizelda.The next day, Carlotta's goons walk through the streets of Mortville delivering a "royal proclaimation" from Carlotta declaring the day "Backwards Day". All residents of Mortville are to walk backwards and wear their clothes backwards or face immediate execution. Muffy and Mole are extremely agitated by this, coupled with the fact that they are hungry from a lack of food. A cat brings a dead rat in and Mole reacts joyfully, cooking the rat and planning on eating it. They later leave the house and head off on an errand; Peggy and Grizelda appear and beg to tag along. Mole's errand is to collect a current newspaper (which is considered contraband) so she can check the lottery numbers. They stop at Mortville's nudist colony to find out where they can score a newspaper, and they are immediately joined by Princess Coo-Coo; when they all fall their knees as instructed by the Queen, Coo-Coo urges them not to. "I'm not like my mother," she claims. Coo-Coo has come to visit Herbert, who is also a nudist, but the goons appear and shoot Herbert dead. Panic ensues, and Peggy, Grizelda, Mole, and Muffy all hurriedly leave the nudist colony and head for a lesbian bar. Inside the bar, a stripper named Flipper (Cookie Mueller) is dancing and beating a bound man to death while the audience cheers her on. Peggy makes a detour to the ladies room, and she is approached for sex by a deranged-looking woman (Pat Moran). When she returns to the table, she begs Grizelda to take her home; Muffy and Mole wonder why she was so adamant to go with them in the first place.Mole and Muffy visit Flipper's girlfriend, Shotsie (Sharon Niesp), and get a contraband newspaper from her. They discover that they are holding the winning lottery ticket after all. Back at the house, Peggy and Grizelda find Coo-Coo in their shed, in a romantic embrace with Herbert's dead body. Grizelda tries to comfort her and Peggy reacts wtih both disgust and jealousy. Peggy opens the door and screams for Carlotta's goons, giving away the location of the Princess; a fight ensues, and Grizelda attacks the goons inside the shed. Although she overpowers them, the small structure collapses and kills her.The goons kidnap Coo-Coo and Peggy and take them before the Queen. The Queen disowns Coo-Coo, who is now blind with rage over the murder of Herbert, and Carlotta orders her to be imprisoned and raped by the goons. Carlotta rewards Peggy for her loyalty by making her the new Princess, grooming her to become the next tyrannical monarch of Mortville. She gives Peggy the task of infecting the citizens of Mortville with rabies, starting with Coo-Coo; Peggy injects her with rabies and throws her out into the streets to spread the disease.Meanwhile, Mole goes into Baltimore to collect her lottery winnings; once she has the cash (which totals about $1000), she visits the John Hopkins hospital and demands an immediate sex change. When the nurses and doctor don't cooperate at first, Mole holds them at knifepoint until they comply. When she returns to Mortville, she showers Muffy with presents, including a new bra and a fur coat. She also shows Muffy a large cache of firearms that she has purchased, with which they can rebel against Queen Carlotta and her goons. Mole's final surprise, her sex change, causes Muffy to react in horror; when Mole tries to have sex with Muffy using her new penis, Muffy vomits and insists that Mole cut it off, which she does. Muffy sews up the wound dutifully, saying that she only pretended to want a man to make Mole jealous, and she vows to stay by Mole even though she now has no sex organs.Shotsie and Flipper appear with the now very ill Coo-Coo, and they hatch a plan to overturn Carlotta. Muffy acts as a decoy and seduces the castle guard, who is ambushed and murdered by Mole and the others. As Carlotta and Peggy gloat in Carlotta's bedroom about the success of their rabies plan, the rebels go into the castle and execute Carlotta's guards, confronting Peggy and Carlotta at gunpoint. They force Carlotta to kiss Muffy's ass, then let Coo-Coo bite her, infecting her with rabies. Peggy tries to act as if she's been forced to do what she did, but everyone sees through her and Mole executes her as well. They decide to cook and eat Carlotta, emerging from the castle with Carlotta's body roasted and dressed out like a roast pig. As Coo-Coo convulses and dies, the citizens of Mortville all appear and help eat the evil Queen in celebration (implying that they will all be infected with rabies as well).