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| Uma Thurman | Sissy Hankshaw |
| John Hurt | The Countess |
| Rain Phoenix | Bonanza Jellybean |
| Lorraine Bracco | Delores Del Ruby |
| Angie Dickinson | Miss Adrian |
| Roseanne Arnold | Madame Zoe |
| Keanu Reeves | Julian Gitche |
| Noriyuki ``Pat'' Morita | The Chink |
| Sean Young | Marie Barth |
| Crispin Glover | Howard Barth |
| Ed Begley Jr. | Rupert |
| Heather Graham | Cowgirl Heather |
| Victoria Williams | Cowgirl Debbie |
| Carol Kane | Carla |
| Grace Zabriskie | Mrs. Hankshaw |
| William Burroughs | Himself |
A beautiful young woman with unusually big thumbs, Sissy Hankshaw decides, fittingly enough, to become a hitchhiker. After finding work as a model for feminine products, Sissy goes to shoot an ad at the Rubber Rose, a ranch owned by the Countess, the company's flamboyant cross-dressing head. While at the ranch, Sissy meets numerous other eccentric characters, including an outgoing and rebellious cowgirl named Bonanza Jellybean .
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