Scientist Dr. Sebastian Caine (Kevin Bacon) creates a groundbreaking serum capable of rendering a subject invisible; however, he struggles with reversing the process. One late night, while re-calibrating the molecular structure of the irradiated protein that should restore visibility to a test gorilla, he successfully solves the conundrum and eagerly informs his team’s top executives about his achievement.
Though he devotes most of his waking life to this serum, Sebastian finds himself obsessing over his former girlfriend, Dr. Linda McKay (Elisabeth Shue), who happens to be one of his colleagues. Unbeknownst to him, she has begun a relationship with Dr. Matt Kensington (Josh Brolin), another member of their research team. Alongside fellow veterinarians Sarah Kennedy (Kim Dickens) and Carter Abbey (Greg Grunberg), as well as technicians Frank Chase (Joey Slotnick) and Janice Walton (Mary Randle), they manage to make the serum work on the gorilla. Celebrating their success with a fancy dinner, Sebastian delivers a toast, claiming they are “the finest research group in the world.” Yet, for him, this feels bittersweet as the reversion is his team's final major breakthrough.
Instead of informing the military about the serum’s success, Sebastian chooses to deceive his oversight committee, which includes his former mentor Dr. Howard Kramer (William Devane). He persuades Linda and Matt to join in this deception, and they quickly pivot to human testing, with Sebastian being the subject. After undergoing a painful transformation, he awakens to find that he can see through his eyelids and conducts various self-tests. However, when he tries to revert back to visibility after three days, the outcome fails, leaving him on the brink of death.
Desperate, his colleagues create a crude latex mask for him to wear around the lab, simulating a human form to a certain degree. In time, Matt discovers a potential solution to Sebastian’s visibility issue, but a computer simulation goes awry. As isolation from the lab starts to weigh heavily on Sebastian, his demeanor shifts drastically; he grows increasingly aggressive. Defying orders from Carter, he sneaks back to his apartment, where he gathers books, CDs, and his favorite snack, Twinkies. Temptation soon leads him to spy on his neighbor (Rhona Mitra), culminating in a horrific act of sexual assault.
Meanwhile, Linda discovers Sebastian's mask and clothing abandoned in the apartment, but finds no trace of him. Upon his return to the lab, she warns Sebastian that if he attempts to leave again, she and Matt will alert Dr. Kramer about their actions. Ignoring their threats, he sets up a device that projects a video loop of his heat signature in his quarters to fool Frank into believing he is still in the lab, allowing him to spy on Linda and Matt. Fueled by rage upon discovering their intimacy, Sebastian shatters their bedroom window.
Angry and agitated, Sebastian returns to the lab, struggling to control his emotions as he grapples with the fact that Linda and Matt are together. His frustration escalates when he is disturbed by an invisible dog’s barking, leading him to kill the animal in a brutal display of violence. The team soon realizes they have been misled by Sebastian’s deception, forcing Linda and Matt to confess their involvement to Dr. Kramer. Upon hearing this, he is disappointed and promptly dismisses them from the project. Before he can notify the military, Sebastian, having tailed Linda and Matt, drowns Dr. Kramer in his own swimming pool.
The following day, once all members of the team are present in the lab, Sebastian sabotages their communication and elevator access, rendering them isolated. Stripped of his clothing and mask, he becomes an invisible predator, hunting down his colleagues. As the team frantically searches for him, the tension escalates into chaos. Janice, lagging behind, becomes a victim as he strangles her with an IV line.
The remaining team members, Linda, Matt, Sarah, Carter, and Frank, quickly realize that they are in grave danger, as Sebastian is intent on killing them. Linda, Sarah, and Frank take refuge in the lab while Matt and Carter gear up with tranquilizer guns to seek him out using thermographic goggles. Matt mistakenly shoots at a steam vent, while disaster strikes as Sebastian seizes Carter, yanking him into the air and causing him critical injuries. In the midst of the violence, Sebastian nearly kills Matt, but Linda manages to pull him to safety.
With Sebastian continuing his rampage, Sarah attempts to tend to Carter's wounds, but the situation turns deadly. Sebastian corners her in the freezer, and in a cruel twist, renders her unconscious before inflicting further harm. Linda and Matt discover the aftermath, finding Carter critically injured and Sarah dead in the freezer. As the body count rises, Frank gets caught in Sebastian's wrath, leading to a deadly confrontation.
The stakes heighten as Sebastian locks Linda and Matt in a freezer, turning down the temperature while he prepares to destroy their lab with nitroglycerin. Linda, ever resourceful, uses lab equipment to fashion an electromagnet, risking their lives to escape. As chaos looms, a battle ensues between her and Sebastian, leading to a fierce fight where the consequences of their experiments come to a deadly climax.
Ultimately, in a final confrontation, Linda manages to send Sebastian into the inferno of the exploding lab, a harrowing ending to their dark experiment. Both Linda and Matt emerge from the flames, profoundly changed, as they are whisked away by medics—the echoes of their ordeal forever lingering in their minds.
