Frank DeTorre is an unkempt and slovenly zookeeper at the Sucat Memorial Zoo in Rhode Island. Depressed by the loss of his wife years earlier, he copes by overeating and refusing to exercise, much to the annoyance of his young daughter Shane. Inside his body, or "The City of Frank" as known by its anthropromorphized inhabitants, white blood cell Osmosis "Ozzy" Jones is an over-zealous officer of the Frank Police Department, the city's center for immune responses against bodily threats, who was demoted to patrol duty in the mouth after he induced Frank to vomit against orders. This incident got Frank fired from his previous job at a pea soup factory, and banned from visiting Shane's school due to a restraining order filed by her P.E. and science teacher, Mrs. Boyd.