Frank DeTorri is an unhealthy, sick zookeeper at Sucat Memorial Zoo in Rhode Island. He copes with the sacrifice of his wife Maggie by overeating and foregoing basic hygiene, much to his daughter Shane's embarrassment. Inside his body, called the "City of Frank" by its anthropomorphic inhabitants, white blood cell Osmosis "Ozzy" Jones is a quick-witted officer of the Frank Police Department whose attempts to catch germs end up causing trouble in Frank's body.