Work-at-home scientist Professor Brody (Jeff Goldblum) is developing a formula to cure human allergies to dogs. In the hidden war between dogs and cats, that makes him number one on the feline enemy list. New family pet, young Lou (Tobey McGuire) the Beagle, is blissfully unaware that fluffy but evil Mr. Tinkles (Sean Hayes) has targeted his new family, seeking to steal the formula. His plans to pervert it into something to make humans more allergic to dogs will allow him and his cat followers to rule the world when dogs are banned from human homes. Lou is drafted into the canine counter-espionage world, where he struggles to defeat Mr. Tinkles and his reluctant sidekick, Calico (Jon Lovitz). Despite attacks by cat-ninjas and a Russian Blue explosives expert, young Lou must defeat Mr. Tinkles, while avoiding Mrs. Brody’s (Elizabeth Perkins) anger over “accidents” in the house, and still being Scotty Brody’s (Alexander Pollock) best friend. He is helped out by a disparate pack of canine pals, including stalwart shepherd Butch (Alec Baldwin), sexy Saluki Ivy (Susan Sarandon), clumsy sheepdog Sam (Michael Clarke Duncan), and manic Chinese Hairless electronics whiz Peek (Joe Pantoliano).