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- Johnny Depp as Raoul Duke
- Benicio del Toro as Dr. Gonzo
- Tobey Maguire as The Hitchhiker
- Christina Ricci as Lucy
- Michael Jeter as L. Ron Bumquist
- Craig Bierko as Lacerda
- Ellen Barkin as The Waitress at North Star Cafe
- Gary Busey as The Highway Patrolman
- Cameron Diaz as The Blonde TV Reporter
- Penn Jillette as The Carnie Talker
- Christopher Meloni as Sven
- Harry Dean Stanton as The Judge
- Flea as Hippie
- Jenette Goldstein as Alice the Maid
- Verne Troyer as Wee Waiter