The movie opens in Toronto, 1954 with Elliot and Beverly Mantle (Jonathan and Nicholas Haley) as young boys, discussing sex and trying to learn about the female form. Flash forward to the brothers (Jeremy Irons) at Cambridge, Massachusettes in 1967, working in a medical lab and receiving acclaim for inventing a retracter. We see that they seem to share each other's experiences.
Flash forward another 21 years back to Toronto the present day, and Mantle is examining a movie-star patient, Claire (Genevieve Bujold). She has three openings in her uterus, and it facinates him. The brothers switch appointments regularly, and we see that Elliot is more aggressive and outgoing than Beverly. Elliot encourages Beverly to visit Claire, who obviously had a tryst with Elliot the previous night. Beverly is less willing to be wild, but Elliot reminds him that they always share women.
Beverly falls in love with Claire, and refuses to share his experience with Elliot. Tension between the brothers begins to build. Beverly lets slip to Claire that he has a brother, and gets upset when she teases him. She tells him she thinks he's schizophrenic.
Claire has lunch with Laura (Shirley Douglas), who tells her Beverly and Elliot are twins. Claire realizes she doesn't know who she's sleeping with. When she tells Elliot she knows, he gets agitated, but agrees to allow her to meet both of them. She tells them she knows what they are doing and storms off. Elliot is amused, but Beverly is saddened.
At another awards ceremony, Beverly arrives, drunk, and starts ranting about Elliot taking credit for his work. They reconcile, but Elliot has been offered a job, and Beverly is now taking uppers. Beverly goes to see Claire and apologizes. After sex, he has nightmares about Claire trying to separate him from Elliot. Drug use continues.
Elliot begins his new glamourous work, and has sex with identical twin protitutes, telling them to call him by both his name and his brother's. He shows up at Claire's movie set and tries to dissuade her from seeing Beverly. She tells him he's very different from Beverly, and refuses to sleep with him.
Claire leaves town for contract negotiations, and Beverly continues to take drugs. He calls Claire's hotel and thinks the man (her secretary) who answers is her lover. He tells him of her "mutation". Beverly goes to see Elliot and tells him she's having an affair.
Beverly's work begins to suffer, and he goes to a metalsmith (Stephen Lack) to redesign his medical tools to deal with the "mutations" he is trying to treat. Elliot is now taking more drugs, and the practice is suffering. His secretary quits. He freaks out during an operation while trying to use the new tools.
Elliot tries to cover up. The board doesn't buy it, and the brothers are forced to close their practice.
Elliot continues to date, and gets Beverly to dance with his girlfriend Cary (Heidi Von Palleske). He joins in, and the three of them dance intimately. When Beverly realizes they are trying to seduce him, he breaks away but collapses and is rushed to the hospital. Elliot promises to detox Beverly, so no one will know about the drugs. Beverly is locked in the clinic to dry out.
Elliot's drug use is increasing. Cary tries to tell him he is becoming like Beverly, but Elliot explains that he wants to get "synchronized" with Beverly.
Claire gets back and straightens out the mix-up with her secretary, then tells Beverly to come see her. He has trouble getting out of the locked clinic, but is desperate to see her. On the way, after stopping to be sick on the street, he notices an art exhibit showing the tools he had the metalsmith make. He finally arrives at Claire's and tries to get her to fill a prescription. She doesn't, and Beverly exhibits more confusion. When he returns to the clinic, he finds the office trashed, and Elliot in the shower, wasted.
The brothers agree to try and kick the habit, and Elliot begins to sound like a child. In a drug-induced haze, Beverly operates on his brother, using the customized tools he designed, trying to separate them as siamese twins.
When Beverly awakes, he sees his brother - disemboweled. He packs a bag, gets cleaned up, and leaves, making a phone call to Claire, but when she asks who is calling, he hangs up on her. In a daze, he wanders back upstairs, and collapses, intertwined with his brother.