Spot Helperman (voiced by Nathan Lane) is one smart puppy leading a secret life as Scott Leadready II, the coolest 4th grader in school. It is Spot's ultimate wish that he become a "real boy" like his master Leonard Helperman (voiced by Shawn Flemming). When Leonard and his mother (voiced by Jo Rupp) decide to move to Florida, Spot gets his wish. He hooks up with a mad scientist named Ivan Krank (voiced by Kelsey Grammer), who experiments with turning animals to humans. Spot becomes a canine "guinea pig" in Krank's evolutionary experiment. Although the scientist's theories still have a few "bugs" (mosquito girl and alligator boy), Spot is successfully transformed into a human. But, inevitably, things still do not go as well as planned because Krank fails to calculate "dog years" and Spot finds himself in the body of a middle-aged man. Now it is up to Leonard Helperman, a cat named Mr. Jolly (voiced by David Ogden Stiers) and a boisterous bird name Pretty Boy (voiced by Jerry Stiller) to help Spot out of his "tight spot" and try to right a genetic wrong.