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Chris Rock
Osmosis Jones (voice)
Laurence Fishburne
Thrax (voice)
David Hyde Pierce
Drix (voice)
Brandy Norwood
Leah (voice)
Elena Franklin
Shane Detorre
Bill Murray
Frank Detorre
William Shatner
Mayor Phlegmming (voice)
Ron Howard
Tom Colonic (voice)
Kid Rock
Kidney Rock (voice)
Molly Shannon
Mrs. Boyd
Chris Elliott
Bob
Jonathan Adams
Officer Tom (voice)