The movie opens with the invisible Nick Halloway (Chevy Chase) dictating his memoirs into a video camera. To prove it is not a camera trick, he waves a pencil and the camera remote around to prove they aren't attached to wires. He also chews some gum and blows a bubble. Nick narrates the story of how he came to be invisible, beginning a few days earlier at his job as a stock analyst. His secretary refers to him as a "bullshit artist", and he spends most of his life avoiding responsibility and connections with other people. At his favorite bar, the Academy Club, his friend George Talbot (Michael McKean) invites him to join his table where Nick meets Alice Monroe (Darryl Hannah). Sharing an instant attraction, Nick and Alice make out in the ladies room. When Alice has to leave, Nick drinks heavily to console himself, although the pair set a lunch date for Friday.Hungover the following morning, Nick is unable to avoid going to a shareholder's meeting at Magnascopic Laboratories. Unable to endure the droning presentation by Dr. Bernard Wachs (Jim Norton), Nick leaves in search of a bathroom. When he asks a lab technician for directions, the technician spills coffee onto a computer console. Nick eventually finds an empty sauna and lies down for a nap. Meanwhile, the coffee has caused a meltdown, and the entire building is evacuated. The building seems to explode, but there is no debris. Instead, much of the building is rendered invisible, including Nick.CIA operative David Jenkins (Sam Neill) arrives on the scene to contain the damage, and he discovers Nick's condition. While they are transferring him to an ambulance, the agents joke about how Nick will spend the rest of his life hooked up to machines and studied by scientists. In a panic, Nick flees. Jenkins convinces his supervisor Warren Singleton (Stephen Tobolowsky) not to notify CIA headquarters so that they can capture and take credit for Nick, who could become the greatest secret agent in the world.Nick holes up in his apartment, but Jenkins tracks him down using the guest list for the meeting. Nick decides to hide at the Academy Club. He locates Dr. Wachs in the hope that he can restore Nick's visibility. Unfortunately, Wachs has no idea how to help. After Nick runs, Jenkins arrives and interrogates Wachs with a strong injection and eventually kills him to keep Nick's invisibility a secret.Nick sneaks into Jenkins' office where he finds that Jenkins has a file on him. Before he can study it more closely, Jenkins walks in with a few of his staff and they hold a meeting regarding Nick, Wachs and the incident at Magnascopic. Nick listens closely, finding out that the manhunt for him will never stop, even if it means Jenkins will kill him to keep his accident secret. After the meeting ends, Jenkins works late in his office. When Nick, stiff from sitting silently against the wall, stretches his leg, it pops and Jenkins realizes Nick is in the room. The two argue over Nick's fate, with Nick promising he'll never become the CIA's guinea pig. Jenkins tries in vain to seize Nick but Nick, knowing where Jenkins kept his pistol in his desk, uses it to hold the agent hostage and escape the building.Nick flees to Marin County north of San Francisco to George's beach house. Unfortunately, George arrives with his wife, Alice and another friend to spend the weekend. Nick reveals his condition to Alice, who decides to help him. However Jenkins is able to track him to George's beach house and Nick and Alice are forced to flee. The pair board a train for Mexico, where Nick wants to set up a new life, trading stocks through Alice as a proxy. Jenkins and his men track them down on the train, and during the ensuing confrontation, Nick falls off the train and into a river. He makes his way to the video store, where he tapes his memoirs.At the end of the tape, he records an ultimatum for Jenkins: exchange Alice for the tape, or Nick will give it to the CIA. Jenkins agrees, putting Alice into a cab as his men surround Nick. However, Nick has disguised himself as the cab driver, and George is standing in for Nick in the exchange. Jenkins pursues the cab, which crashes into the back of another vehicle when they spot Nick's makeup-covered head floating down the street. Jenkins chases Nick into a construction site, his suit jacket becoming partially covered in dust, making him visible. He makes it to the top of the building where Jenkins corners him. Feigning that he'll jump and kill himself, Nick holds his dusty blazer near the edge, tricking Jenkins into lunging for him. Jenkins falls to his death. On the street, a tearful Alice discovers Nick's coat and cries over it for a moment before Nick reveals he's still alive. They both slip past the police.In the final scene set months later, Nick and Alice are hiding out in Switzerland, and the film closes with shots of a still invisible Nick skiing down to their chalet, where a pregnant Alice greets him with a kiss.