College student Jeffrey Beaumont (Kyle MacLachlan) returns home after his father has a stroke. When he discovers a severed ear in an abandoned field, Beaumont teams up with detective’s daughter Sandy Williams (Laura Dern) to solve the mystery. They believe beautiful lounge singer Dorothy Vallens (Isabella Rossellini) may be connected with the case, and Beaumont finds himself becoming drawn into her dark, twisted world, where he encounters sexually depraved psychopath Frank Booth (Dennis Hopper).
Hard-as-nails Lily Dillon (Anjelica Huston) works as a swindler for dangerous bookie Bobo (Pat Hingle), probably the only man she fears. Arriving in Los Angeles on “business,” Lily looks up her son, Roy (John Cusack), a small-time con artist content with paltry sleight-of-hand cheats. Roy’s girlfriend, Myra (Annette Bening), looks like an All-American type but is a grifter looking to pull off another big-time con. The convergence of the three hustlers inevitably means trouble for all of them.
Jodie Foster stars as Clarice Starling, a top student at the FBI’s training academy. Jack Crawford (Scott Glenn) wants Clarice to interview Dr. Hannibal Lecter (Anthony Hopkins), a brilliant psychiatrist who is also a violent psychopath, serving life behind bars for various acts of murder and cannibalism. Crawford believes that Lecter may have insight into a case and that Starling, as an attractive young woman, maybe just the bait to draw him out.