Plot
This film begins with the jeep of the Brody family pulling up to the house, with Mrs. Caroline Brody (Elizabeth Perkins) and her son Scott (Alexander Pollock) bringing in the groceries, and the family's Bloodhound named Buddy immediately starts giving chase to a cat. Buddy follows the cat and pursues him through a neighbor's house, until he finds the cat lying dead on the street, obviously faking. The cat gets up and runs away, and a blue van pulls up and kidnaps Buddy.
An Anatolian Shepherd Dog named Butch (voiced by Alec Baldwin) watches from a window, then goes to his doghouse, pressing a blue button, which grants him access to a large techno-network, and tells an agent of Buddy's kidnap. At Intel HQ, the head dog receives the news about Buddy and orders the best agents to accomplish the mission and defeat the cat menace.
Meanwhile at a farm, a small group of Beagle puppies converse and make fun of a younger puppy (voiced by Tobey Maguire), who wants to be free. A group of young black Doberman puppies led by a large Doberman Pinscher force the Beagles to go underground as Mrs. Brody approaches. Mrs. Brody comes into the puppy pen, and the last beagle puppy comes out. She decides to adopt him and takes him home, naming him Lou after Scott sarcastically suggests "Loser".
Scotty puts him outside and a dog biscuit attached to a balloon falls down. Lou goes near it, and Butch comes out and throws a stick at it, making it explode. Butch then takes Lou into Buddy's doghouse, and shows him the network that dog agents use, and takes him to meet some more agents: Peek (voiced by Joe Pantoliano) is a Chinese Crested Dog who works in an underground tube and has computers, radar, sonar, television, communications, satellite, thermal imaging systems, security cameras, and such. Sam (voiced by Michael Clarke Duncan) is a comical Old English Sheepdog. Lou is also briefed on the origins of the war between cats and dogs, which apparently dates all the way back to Ancient Egypt. Butch also mentioned that Buddy was previously on the mission until he was captured by the cats, escaped from them, and retired from the spy business.
Meanwhile, Mr. Tinkles (voiced by Sean Hayes), a white Persian cat plans to conquer the world by making all humans allergic to dogs with Mr. Brody (Jeff Goldblum)'s research on a cure for dog allergies. He is briefly interrupted by Sophie the Maid (Miriam Margoyles) who needs to dress him upon seeing the comatose Mr. Mason (Myron Natwick). He then tells his sidekick Calico (voiced by Jon Lovitz), an Exotic Shorthair, to send in the ninja cats (voiced by Danny Mann and Billy West) he hired to steal the research. He sends in Devon Rex cat ninjas to steal the research but Lou managed to prevent them from stealing the research. Lou then meets an ex-agent dog named Ivy (voiced by Susan Sarandon), a Saluki who belly scratches him. Disappointed that the ninja cats failed him, Mr. Tinkles then orders Calico to send a Russian Blue kitten (voiced by Glenn Ficcara) to steal the research. The Russian then frames Lou for defecating in the house with a ball containing dog feces. He then places a bomb on the lab door. Butch and Lou manage to get into the house.Russian fires a series of boomerangs trashing the Broody's living room in the process. Lou then distracts the Russian while Butch disables the bomb. But the Russian turns his attention on Butch and tries to kill him. Butch gets caught in a telephone wire but manages to escape and disables the bomb. But the Russian holds out a remote that will explode the bomb and laughs until the lab door hits him. The Russian is captured and interrogated. The agent tells the gang that they pumped a few things out of the Russian's stomach, including a note written by Mr. Tinkles.
After an incident with Lou playing with Scott, Professor Brody's machine finally gets the positive combinations for the formula. As Mr. Tinkles and Calico overhear the call between Professor Brody and another person, they decide to spring a trap for Dr. Brody and his family. First Mr. Tinkles makes his sinister side known to Sophie causing her to faint. Then he and his cats take Mr. Mason's comatose body to Mason's industries where Mr. Tinkles passes his voice off as Mr. Mason to send the employees home and commandeer the factory for the next plot.
While trying to decipher Mr. Tinkles location, the dogs are unaware that the Brody's have been led into a trap and are kidnapped by the said cat. After receiving a video from the cat demanding Mr. Brody's research as a ransom, the dogs from around the world meet up at a meeting run by the Mastiff (voiced by Charlton Heston). When the dog agents are unable to give up the formula after the metting of the world's dogs, Lou gives in and brings Mr. Tinkles the research and is betrayed. Butch manages to find the depressed Lou, and the two along with Ivy stage an ambush of Mr. Tinkles factory (where the latter plans to use mice to spread the now mass produced allergy to dogs). While Butch, Ivy, Peek, and Sam fight Tinkle's cat forces, Lou frees the Brodys and Calico (who was betrayed by Tinkles), revealing he can speak in the process. But Tinkles traps Butch as he goes looking for Lou and almost kills him. Lou defeats Tinkles and rescues Butch, but the claw of an excavator hits his head and a flocking tank, causing an explosion that destroys the factory. Butch manages to save Lou, but Lou is unresponsive. After a few heartful moments of sadness, Lou awakens and all rejoice. Lou decides to be a normal dog and not an agent. As for Mr. Tinkles, he is sent to live with Sophie and her sisters who dress him in ridiculous outfits.
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