Unknown to humans, a secret war has been raging between cats and dogs for eons, but a fragile truce has long held the order of the animal kingdom in place. Now the balance of power has tipped, as a researcher, Professor Brody (Jeff Goldblum), is about to invent a vaccine that will erase all human allergies to dogs. This is too much for the autocratic Mr. Tinkles (Sean Hayes), a white Persian kitty bent on world domination. The Brody home becomes ground zero for the renewed conflict between feline and canine, with a young Beagle puppy named Lou (Tobey Maguire) caught in the middle as the new point man for his species' cause.