Frank DeTorre is an unkempt
zookeeper at the Sucat Memorial Zoo in
Rhode Island. He copes with his late wife's death by overeating and foregoing basic hygiene, much to the concern of his daughter Shane. Inside his body,
white blood cell Osmosis "Ozzy" Jones is an overzealous officer for the "Frank Police Department," Frank's
immune system.
Incumbent mayor Phlegmming doubles down on his
junk food policies, so he could go to a
food festival in
Buffalo, New York, ignoring its effects on Frank's health. This causes Frank to eat a filth-covered
boiled egg, allowing Thrax, a deadly
virus known mainly as "The Red Death", to enter his body and inflame his throat. Phlegmming instructs Frank to take a cold pill, Special Agent Drixenol "Drix" Drixobenzometaphedramine, who proceeds to disinfect the throat, covering up evidence of Thrax's arrival. Ozzy is told to assist Drix in his investigation, much to his displeasure. Thrax assumes leadership of a gang of sweat germs and breaks down Frank's mucus dam, nearly killing the duo and inciting a
runny nose. Ozzy tells Drix how he once caused Frank to
vomit on Shane’s teacher Mrs. Boyd at a school
science fair after Frank ate a contaminated
oyster which led to Frank's
dismissal from his previous job and Mrs. Boyd filing a
restraining order against him while her three children endure constant teasing from other children and keep transferring schools; Frank’s brother Bob had gotten him his job at the zoo and Ozzy was suspended for unnecessary force. Ozzy and Drix visit Chill, a
flu vaccine and
informant, who directs them to Thrax's hideout in a germ-ridden
nightclub in a large
zit on Frank's forehead. Ozzy goes undercover and infiltrates Thrax's gang, where he learns that Thrax intends to masquerade as a
common cold and use his knowledge of
DNA to kill Frank. When Ozzy is discovered, Drix comes to his aid, causing a brawl which culminates in the zit being popped in the chaos. Its
pus lands on Mrs. Boyd's lip during a meeting between her and Frank when he attempts to have the restraining order temporarily lifted so he can attend a school trip with his daughter; in response, Phlegmming closes the investigation, dismisses Ozzy from the police force and orders Drix to leave Frank’s body. Outside, Frank prepares to go to Buffalo, much to Shane's disapproval. Unbeknownst to the duo, Thrax has survived the zit's destruction and launches a lone assault on the
hypothalamus where he steals a crucial
nucleotide. He then abducts Phlegmming's secretary, Leah Estrogen, and flees to the mouth to escape. His actions disable the body's ability to regulate the body's internal temperature and Frank develops a dangerous
fever. As Frank is hospitalized, Ozzy convinces Drix not to leave and the duo catch up to Thrax and rescue Leah. Thrax induces Frank to sneeze him out of the mouth using
pollen. Drix shoots Ozzy after him and he and Thrax both land on Shane's
cornea. As the duo battle, they end up on one of Shane's
false eyelashes. Ozzy tricks Thrax into getting his hand embedded in the lash and escapes just as it falls into a
beaker of
rubbing alcohol, killing Thrax. As Frank's temperature surpasses Fever#Hyperpyrexia|, he goes into
cardiac arrest. Riding on one of Shane's tears as she mourns her father, Ozzy falls back into Frank's mouth with the stolen nucleotide, reviving him just in time. Ozzy is then welcomed back into the police force as he begins a relationship with Leah and Drix stays as Ozzy's new partner, whereas Frank commits himself to living a healthier lifestyle. Phlegmming, now removed from office and reduced to janitorial duty in the bowels, ejects himself from Frank’s body via
flatulence after ignoring a notice not to trigger it. ==Cast==