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| Brendan Fraser | Stu Miley |
| Bridget Fonda | Julie McElroy |
| Rose McGowan | Kitty |
| Whoopi Goldberg | Death |
| Chris Kattan | Organ Donor Stu |
| Dave Foley | Herb |
| Megan Mullally | Kimmy |
| Jamie Donovan | Reporter #1 |
| Amy Higgins | Clarissa |
| Allan Trautman | BBQ Pig |
| Owen Masterson | Jack the Ripper |
| Randall Bosley | Fred |
| Giancarlo Esposito | Hypnos |
| Arturo Gil | Rat Guard |
| Paul Guiles | Reporter #2 |
| Shawnee Free Jones | Lizzie Borden |
| Harry Jay Knowles | Lucky |
| Jason Kravits | Guest |
| Pons Maar | Lead Puppeteer |
| Skyler Marshall | Janitor |
| Mary Stein | Lulu |
| John Turturro | Monkeybone |
Slipping into a coma following a freakish accident, cartoonist Stu Miley finds himself in an incredible fantasy world known as Down Town. To return to reality, Stu has to outwit Death, herself ... but one of the cartoonist's own creations, Monkeybone, has come to life and is manically intent on destroying Stu's plans to resume his life.
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