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| Andy Samberg | Ham III |
| Cheryl Hines | Luna |
| Kenan Thompson | Ringmaster |
| Stanley Tucci | The Senator |
| Kristin Chenoweth | Kilowatt |
| Patrick Warburton | Titan |
| Jeff Daniels | Zartog |
| Omid Abtahi | Dr. Jagu |
| Patrick Breen | Dr. Bob |
| Carlos Alazraqui | Houston |
| Kath Soucie | Dr. Smothers |
| Jane Lynch | Dr. Poole |
Ham III is the grandson of the first chimpanzee who first blasted into outer space. He and two other chimp astronauts go on a dangerous mission through a black hole. Landing on an inhabited planet, the space-faring simians must help depose a planetary tyrant, then find a way back to their own world.
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