Frank Detorri (BILL MURRAY) is not a healthy guy. He knows it, his young daughter Shane (ELENA FRANKLIN) and her teacher Mrs. Boyd (MOLLY SHANNON) know it, his buddy Bob (CHRIS ELLIOTT) knows it – pretty much anyone who looks at Frank knows he’s no fitness poster boy. Frank eats junk food, abstains from exercise, and treats his body like anything but a temple, particularly since the death of his wife, Shane’s mother.
This unhealthy approach to life makes the inside of Frank’s body a bacterial battleground that festers until the day he invokes his ten-second rule ("If food hits the ground and you pick it up within ten seconds, you can eat it") on a hard-boiled egg he scoops off the ground at the zoo where he works. As he opens his mouth to ingest the dirty egg we follow right along, travelling down into his swampy insides to discover… thanks to the magic of Hollywood’s top animators, colorists and CGI artists…
The City of Frank: a pulsing, organic living metropolis that is home to an entire society of characters – cops, crooks, government officials, deadbeats, villains, and femme fatales. Frank’s got it all, and he’s got it bad.
Fortunately for Frank, one of his internal inhabitants is Osmosis Jones (CHRIS ROCK), a young white blood cell and an officer of the FrankPD. Jones sees an opportunity to make good on his troubled past when he senses the stirrings of a fatal illness spreading through Frank – a villainous virus that goes by the name of Thrax (LAURENCE FISHBURNE). But to bust Thrax, Jones will have to bypass Mayor Phlegmming (WILLIAM SHATNER), a fat-cat brain cell who gives the citizens what they want, not necessarily what’s good for them – like the upcoming Buffalo Wings Festival trip. "A fat Frank is a happy Frank," is the mayor’s motto.
Luckily, the Mayor’s assistant, a sassy little red blood cell named Leah (BRANDY NORWOOD), does want what’s best for Frank, even if her only hope rests with the bumbling Osmosis Jones. And Jones finds another unlikely ally in the visiting Drix (DAVID HYDE PIERCE), a Drixenol cold tablet with twelve hours of time-released germ-fighting power.
Meanwhile, Frank himself does nothing to help from the outside. He’s too busy trying to be there for his daughter as she adjusts to life without Mom, even though he’s clearly not feeling so hot. Unaware of the germ warfare being waged inside him, he feverishly plods along until Thrax and Osmosis clash in a deadly battle that brings them to the brink of the outside world, perched precariously on Shane’s eyelashes. As the virus brings Frank down, the two worlds – inside and out – collide in a final battle for Frank’s life, and for the lives of the citizens of Frank!
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