Once-wealthy string magnate Rudolf Smuntz (William Hickey) dies, and he leaves his factory to his two sons, the well-meaning and optimistic Lars (Lee Evans), and venal cynic Ernest “Ernie” (Nathan Lane), who has ignored the family business to become a chef. When Lars refuses a buyout from a cord company called Zeppco, his money-hungry wife April (Vicki Lewis) throws him out and ran off with a wealthy magician. Meanwhile, at Ernie’s restaurant, the mayor is dining and suffers a fatal heart attack when he accidentally eats a cockroach, getting the restaurant closed down. With nowhere left to go, the two brothers take refuge in a property their father left them, an abandoned mansion on the outskirts of town. While attempting to sleep, the two are bothered by a mouse and, when investigating him, find blueprints of the house.
The two discover from the blueprints that the property was built by famed architect Charles Lyle LaRue and would be worth a fortune if properly restored. Ernie and Lars decide to restore the property and auction it to recover their lives. During the renovations the two destroy the mouse’s home, prompting the mouse to take revenge and sabotage their construction efforts. Conventional methods to get rid of the mouse fail as he repeatedly outwits the brothers. They resort to increasingly drastic methods to remove the mouse, including buying a psychotic cat named “Catzilla”, whom the mouse drops down a dumbwaiter to his defeat, and then hiring an eccentric exterminator named Caesar (Christopher Walken). Meanwhile, the two brothers discover the house has an unpaid mortgage on it they cannot pay off and, because of their inability to pay the string factory’s workers, the workers go on strike.
Ernie learns about Zeppco’s offer to buy the factory and secretly plans to accept the deal. While Caesar is working, Lars goes to the string factory to make enough string to pay off the mortgage, in the process getting stripped completely naked, and is met by April who learned about the house’s worth and takes him back. Ernie’s attempt to meet with Zeppco’s representatives fails when he is hit by a bus while trying to impress two Belgian hair models, Ingrid (Debra Christofferson) and Hilde (Camilla Søeberg). Lars informs him that April has given them the money to pay off the mortgage, but the two return to the house to find it further destroyed by Catzilla and Caesar traumatized from the mouse dragging him through the house by his truck winch.
The brothers resume their crusade against the mouse, accidentally destroying part of the floor with a bug bomb Caesar left behind, and then turn on each other when they overhear a voicemail exposing Ernie’s attempt to secretly sell the factory and Lars previously turning down their offer. During their argument Ernie ducks from an orange thrown by Lars, which hits and stuns the mouse. The two cannot bring themselves to finish him off, and they seal him in a box mailed to Cuba. The brothers reconcile and finish their renovations. The night of the auction, Lars discovers the mouse’s box, returned due to insufficient postage and with a hole gnawed out of it (as Lars forgot to weigh the mouse). As the auction progresses, the brothers attempt to flush out the mouse by feeding a garden hose into the wall, causing the house to explosively flood and then collapse as the buyers flee. April leaves with a wealthy bidder and the brothers take solace in the assurance the mouse must have perished in the collapse.
The brothers sleep the night in the factory, unaware the mouse has followed them. Witnessing their sorry state, the mouse activates the factory’s machinery and drops a chunk of cheese into it, producing a ball of string cheese. Inspired, the brothers renovate the factory to focus on producing string cheese, with Lars running the factory while getting a new girlfriend, Ernie as his chef, and the mouse as their taste tester for new flavors.