Set in London, the film opens with American best-seller author Catherine Tramell (Sharon Stone) in a speeding car with her companion, a famous English football star. Tramell takes the man's hand and begins masturbating with it, all the while increasing her vehicle's speed. At the point of orgasm, Tramell veers off the road and crashes into the West India Docks in Canary Wharf. She attempts to save her partner but, as she says in the subsequent scene, "When it came down to it, I guess my life was more important to me than his."
Tramell is interrogated by Detective Supt. Roy Washburn (David Thewlis) of Scotland Yard. He claims that D-Tubocurarine (a neuromuscular blocking agent, used to relax muscles during general anesthesia) was found in her car, and that a man named "Dickie Pap" said that he sold Tramell "15 milliliters of DTC last Thursday." Tramell counters by saying that this Dickie Pap must be lying because "you’ve got him on some other charge and he's trying to deal his way out, if he even exists."
Tramell begins therapy sessions with Dr. Michael Glass (David Morrissey), who has conducted a court-ordered psychiatric exam and given testimony in her case. Dr. Glass strongly suspects that Catherine Tramell is a superficial sociopath incapable of telling the difference between right and wrong. Tramell begins to play psychological games with Glass, who becomes increasingly frustrated with, yet intrigued by, this mysterious woman. Soon, Glass's own life begins a spiral of destruction.
One night, while having sexual intercourse with a woman, Michelle Broadwin (Flora Montgomery), Glass makes love with a violent aggression after dealings with Tramell, similar in the fashion that Michael Douglas's character Nick Curran did to police psychologist Dr. Beth Garner in the original Basic Instinct. Glass receives a phone call from his ex-wife in a state of distress. Her partner, a journalist writing a negative story about Glass, has been found dead. Glass suspects that Tramell committed the murder and is attempting to frame him for it. More murders begin to surface around Glass as his obsession with Tramell grows and his career and life are threatened until he himself can no longer tell right from wrong.
Things come to a head during a confrontation between Glass and Tramell at her apartment where after a struggle Glass attempts to kill Tramell. Tramell gives Dr. Glass a copy of the draft of her next novel titled "The Analyst". After reading it, he realizes that Catherine has novelized most of the recent events including herself and other people related to Dr. Glass, even himself, as characters. Then it turns out that the character based in herself is going to kill a therapist based on Glass's colleague, Dr. Gardosh.
Glass runs to Dr. Gardosh's apartment to warn her, finding Catherine there to his dismay. Dr. Gardosh tells him that he is not in charge with Tramell's therapy anymore and that he's going to have his professional license revoked, due to bad praxis regarding Tramell's treatment. There is a struggle between Glass and Gardosh and the latest results knocked out. Catherine threatens Glass with a gun she carries for protection, but Dr. Glass takes it away from her. When Detective Washburn arrives to the scene, Glass kills him because Catherine told him he had killed the girlfriend of one of Glass's patients who was a drug dealer just to "nail him", situation that carried a lot of trouble for Glass in the past.
In the final scene, Tramell pays a visit to Glass at a local mental hospital where he, silent and institutionalized, learns from her that the subject of her latest best-selling novel was, as with Curran back in San Francisco, a man very much like him. Tramell psychologically manipulated Glass into committing all those murders for her own self-amusement. Tramell leaves with a very wicked smirk on her face while Glass continues to sit silently in his wheelchair with unmistakable frustration and rage.
