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Synopsis
Eleanor and Frederick Little and their young son George are intending to adopt. While George is at school, his parents go to an orphanage where they meet an anthropomorphic teenage mouse named Stuart. Despite misgivings from Mrs. Keeper, they adopt Stuart and take him home. However, Stuart is greeted coldly by George, who refuses to acknowledge the mouse as his brother, and the family cat Snowbell, who is disgusted at having a mouse for a "master". Despite Eleanor and Frederick's intentions, Stuart quickly feels like an outsider in the large Little family, especially when their relatives bring Stuart large presents and George snaps at his family, claiming that Stuart is not his brother. When Stuart admits his feelings of loneliness to his parents, they ask Mrs. Keeper to do some background research on Stuart's biological family.
After accidentally stumbling across George's playroom in the basement, Stuart finally bonds with George when they play together and plan to finish George's remote controlled boat, the Wasp, for an upcoming boat race in Central Park. At the same time, however, one of Snowbell's alley cat friends, Monty, visits unexpectedly and discovers Stuart. Determined not to have his reputation destroyed, Snowbell meets with Monty's leader, Smokey, a mafia don-like Russian Blue, and plots revenge to have Stuart removed from the household.
Stuart and George finish the Wasp in time for the race, but on the day of the race, the controller is smashed when a bystander accidentally steps on it. Stuart pilots the Wasp himself, but ends up in a tussle with a larger boat belonging to George's rival, Anton, who has already wiped out the other boats. Stuart snaps the wires of Anton's boat and wins the race, finally winning George's respect. During the family celebration, the Littles are visited by a mouse couple, Reginald and Camille Stout, who claim to be Stuart's parents who gave him up to the orphanage years ago due to poverty. Reluctantly, Stuart leaves with the Stouts, George presenting him a toy car as a farewell gift. A few days later, however, Mrs. Keeper arrives to tell the Littles that Stuart's parents actually died years ago in a supermarket accident, prompting them to call the police believing he was kidnapped.
Meanwhile, Snowbell meets with Smokey and the alley cats, who reveal that they had forced the Stouts to pose as Stuart's parents, in order to remove Stuart from the household. Fearing retribution should the Littles discover Snowbell's deception, Smokey orders the Stouts to hand Stuart over to them. But the Stouts, having grown to love Stuart like their own, tell him the truth and instruct him to escape. Furious, Smokey orders a manhunt for Stuart, with the other cats (minus Snowbell and Monty) cornering him in Central Park and causing a chase. Despite losing his car and almost falling down a storm drain, Stuart manages to evade Smokey's gang and return home, despite the Littles having put up posters of him all over the city. The only one present is Snowbell, who lies that the Littles have been enjoying themselves greatly since Stuart's departure, and uses his removed face from the family photograph as proof (which was actually used for the posters). Heartbroken, Stuart leaves the house again.
When the Littles return home with no success of finding Stuart, Snowbell begins to realize his selfishness and starts to feel incredibly guilty for everything he's done. Later, Smokey, Monty and the other alley cats pinpoint Stuart's location back to Central Park and bring Snowbell along for the hunt. Snowbell finds Stuart in an empty bird's nest and saves him from the cats, confessing that the Littles truly do love him. Smokey, Monty and the other cats eventually catch up and corner Stuart on a branch. Before the cats can catch him, Snowbell breaks the branch they are standing on, sending them (Monty included) falling into the river below. Smokey then tries to ambush Snowbell from behind, but Stuart hits him off the tree with another branch. Smokey then leaves angrily, but is chased off by stray dogs as Stuart and Snowbell return home and reunite with the Little family.
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