The basic premise is that Mickey Mouse and his friends run a nightclub called the "House of Mouse," which shows Disney cartoons as part of its floor show.
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Some episodes have specific themes (such as technology), with cartoons to fit that episode's theme. The theme is usually not beneficial to at least one character, usually Donald.

Many characters from Disney animated films (such as Aladdin, Pinocchio, Peter Pan, Hercules and many more) have appeared on House of Mouse, mostly as guests and attendees. The show is notable for including many relatively obscure and otherwise rarely used Disney characters, often with speaking parts. Mickey is the club's owner, while Minnie Mouse manages the finances and show production. Other House of Mouse staff members include greeter and co-owner Donald Duck, reservation clerk Daisy Duck, head waiter Goofy, mascot Pluto, mechanical technician Horace Horsecollar, chef Gus Goose, gossip columnist Clarabelle Cow and parking valet driver Max Goof. A musical band consisting of Huey, Dewey, and Louie, with such alternating names as "The Quackstreet Boys" and "The Splashing Pumpkins", regularly performs. Pete is club's greedy landlord, who often attempts to shut the club down for his own purposes by sabotaging the show, as Mickey's contract states that the club stays open only as long as the show goes on.

Each episode explores the comic mishaps of Mickey and associates running the club, which are used as wraparounds for Disney cartoons (some of which are classic theatrical cartoons from the 1930s, 1940s and 1950s, but most of which are reruns from Mickey Mouse Works).

The show was produced by Walt Disney Television, and originally aired from 2001 to 2004 and ran for 52 episodes [1]. The show is one of many Disney cartoon series made in Widescreen HD format.

House of Mouse aired on One Saturday Morning on ABC. As of February 2006, this show is no longer airing on The Disney Channel in the US, although it still airs regularly on the Disney Cinemagic channel, which is part of the Disney Channel in the UK. Reruns still air in syndication on Toon Disney.

The theme song is performed by Brian Setzer.