Sebastian Caine (KEVIN BACON), his ex-girlfriend, Linda McKay (ELISABETH SHUE), and her new lover, Matthew Kensington (JOSH BROLIN), are running a top-secret government research project hoping to unlock the keys to rendering someone invisible and then returning them to their natural state.
Working under the direction of Dr. Arthur Kramer (WILLIAM DEVANE) who heads a Pentagon committee overseeing the project, and aided by veterinarian Sarah Kennedy (KIM DICKENS), lab technician Carter Abbey (GREG GRUNBERG), and data analysts Frank Chase (JOEY SLOTNICK) and Janice Walton (MARY RANDLE), the team has succeeded in making a gorilla invisible and then visible again.
Despite the inherent medical danger of doing so and without Kramer's permission or knowledge, Sebastian decides it's time to move on to stage three which involves turning a person invisible. Ever the brilliant egomaniac, Sebastian decides to be the human guinea pig. Their experiment is successful, but after several days of testing, data collection and pranks courtesy of the invisible man, the team realizes that they didn't make the correct calculations to return Sebastian back to visible form.
As they race to do just that, both the effects of the serum and the fact that he's isolated in their underground lab begins to make Sebastian mentally unbalanced. Realizing they have to pull the plug on the project and get Sebastian outside help, the team sets into a motion a series of events that will ultimately endanger their lives as the progressively unstable Sebastian loses his sense of morality but gains a warped sense of limitless power and will do anything to stop the others.