| Eddie Murphy | Professor Sherman Klump/Clesius "Papa" Klump/Young Clesius Klump/Mama Klump/Ernie Klump/Grandma Klump/Buddy Love/Lance Perkins |
| Janet Jackson | Professor Denise Gaines |
| Larry Miller | Dean Richmond |
| John Ales | Jason |
| Richard Gant | Mr. Gaines |
| Anna Maria Horsford | Mrs. Gaines |
| Melinda McGraw | Leanne Guilford |
| Jamal Mixon | Ernie Klump Jr. |
| Gabriel Williams | Isaac |
In an attempt to remove Buddy Love from his subconscious, professor Klump accidentally creates him as a separate person.
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