At the funeral for string magnate Rudolf Smuntz, his two sons - dutiful kid Lars and estranged restaurateur Ernie - serve as two of the coffin-bearers. While carrying their father down the cathedral steps, Lars accuses Ernie of not holding the coffin up, and then the brothers get into an argument over the color of Lars’s suit. During the course of this argument, Lars accidentally wrenches his handle off of the coffin, inadvertently causing the rest of the mourners to drop it onto the steps; Rudolf subsequently slides down them, hits the hearse and gets catapulted into an open manhole. And thus our protagonists’ characters and the overall tone of the film are established.
Following the funeral, the brothers meet with their late father’s lawyer in Rudolf’s old office, a Creepy Changing Painting of Rudolf watching over the three. The lawyer informs them that as per their father’s will, they will be inheriting both his collection of keepsakes and his (now very much antiquated) string factory, which he intended for his sons to run together. Ernie is contemptuous of the notion; besides his disdain for his father, he sees the factory as having no financial worth whatsoever. The brothers also inherit an old, run-down Victorian mansion which Rudolf acquired as payment of a debt, but Ernie dismisses it as being equally worthless after learning that it is only worth $50,000. He then leaves the meeting, taking with him a box of cuban cigars from Rudolf’s keepsakes.
Ernie later hosts the city mayor and his family at his restaurant that evening, but a cockroach crawls out of the cigar box and gets into the mayor’s food during service. The mayor dies of a heart attack after discovering and ingesting half of the roach, with Ernie being blamed for the fiasco and losing his restaurant as a result. Around roughly the same time, Lars is visited by two representatives of Zeppco International, a cord company that has been trying to buy the factory for years. The representatives offer him a hefty cash payment in exchange for the factory, but Lars refuses, having promised his father on his deathbed that he would never sell it to a big conglomerate. He is consequently thrown out of his house by his openly Gold Digger wife April after she learns he turned down the sale.
The two brothers reunite when Lars heads to the diner Ernie now works at, and with no other options between them, they head to the mansion that night. Hearing noises coming from the attic, they go up to investigate, finding the source of the noises to be a seemingly innocuous mouse. They also discover a set of blueprints that reveal the mansion to be the final work of famous architect Charles Lyle LaRue, making it worth a fortune. Eccentric Millionaire and LaRue fanboy Alexander Falko offers to buy the mansion from them, but Ernie decides to auction it off instead, believing this will net them a higher price.
It seems the brothers’ problems are over, but Ernie feels a need to get rid of the mouse he and Lars found earlier, not wanting to risk another event like the cockroach incident. He rigs up a mousetrap at the mouse’s hole, but the mouse manages to snap the trap without getting caught. Ernie suspects that the trap snapped itself when he and Lars investigate the next morning, and later discovers the mouse in a cereal box while getting breakfast. The brothers attempt to kill the mouse with a broom and meat tenderizer, only for Lars to accidentally wallop Ernie’s hand with the latter weapon. Ernie responds by rigging up three mousetraps outside the mouse’s hole; the mouse steals his wheel of gouda cheese.
The brothers get to work on restoring the mansion, during which the mouse is nearly inadvertently killed while Lars is nailing up a piece of wood, escaping death only when Ernie calls his brother to help carry a recently purchased jacuzzi tub - which he spent the last of their money on - up to the bathroom. The mouse startles both brothers into falling into the tub, which is sent sliding out of the house and into an icy lake. Both brothers survive, and Ernie rigs up enough mouse traps to cover the entire kitchen and dining room floor; even if the mouse can safely trigger one, doing so here will set off all the others in a chain reaction, practically guaranteeing the mouse’s capture. The mouse inexplicably manages to lock them in the booby-trapped area for the night though, and uses a spoon to launch a cherry into the mass of traps the next morning, setting them off on the brothers instead.
The mouse then moves to loot the kitchen of the food used in the traps, but Ernie gives chase with a vacuum cleaner, pursuing the mouse back to its hole. The mouse manages to connect the nozzle of the vacuum with a sewage line, causing the vacuum bag to fill up with waste and explode all over the kitchen. As if things weren’t already crap enough for the brothers, an official from the bank comes by and informs them that the house is mortgaged, and that it will be repossessed in two days unless they can pay $1,200.
For their next attempt, the brothers go the logical route of getting a cat to deal with the mouse. To be extra-extra sure of success, they pick a feline named Catzilla, who has previously no-sold being gassed to death, and needs to be kept chained inside a wooden box, with occasional use of a cattle prod. Leaving Catzilla within the mansion, the brothers turn their attention to their $1,200 shortfall. Lars unsuccessfully attempts to persuade his workers to forgo their next couple of paychecks so that he and Ernie can pay off the bank, but only provokes them to go on strike, much to his late father’s disapproval. As he does this, Ernie looks around the office, and discovers documents detailing Zeppco’s attempt to buy the factory. Back at the mansion, the mouse manages to lure Catzilla into a dumbwaiter and chews through its cable, dropping the monstrous cat to its death.
The brothers then hire an eccentric exterminator named Caesar - played by none other than Christopher Walken - to get rid of the mouse, but the mouse manages to hitch Caesar to his truck’s winch line and activate it, dragging the exterminator through the mansion and ripping up large parts of the floor. Meanwhile, Lars attempts to work the factory by himself in order to raise the $1,200, but a series of Stripping Snags lead to him losing all of his clothes in the machinery. At the same time, Ernie tries to meet with the Zeppco representatives and sell them the factory, but he is distracted before their arrival by a pair of attractive Belgian hair models named Hilde and Ingrid, and his goofing off with them leads to him being hit by a bus and hospitalized. In the end, April learns about the auction and provides the brothers with the needed money, while also getting back together with Lars now that he’s a millionaire in the making (Lars for his part is utterly oblivious to her motive).
Returning to the mansion after all of this, the brothers nearly confess about their respective dealings regarding Zeppco and the factory, but discover a now insane Caesar being wheeled out by paramedics, having failed to kill the mouse and been found locked in a trunk in the mansion’s attic. They discover the mouse in the kitchen soon afterwards, but another attempt to catch it leads to Ernie getting stuck in the mansion chimney, and Lars being tricked into causing a gas explosion; Ernie gets blasted out of the chimney and into the icy lake, while Lars is launched into a wooden cabinet that then falls on top of him.
Both brothers survive once again, but Ernie, now fully at the end of his rope, returns to the mansion and attempts to kill the mouse with a shotgun. With Lars goading him on, he ends up shooting a flea bomb that Caesar had dropped earlier, obliterating a huge chunk of the floor and dropping the brothers into the basement. As the two recover from this latest defeat, the Zeppco reps phone up to tell them that they are no longer interested in buying the factory, what with Ernie standing them up for over an hour, and Lars turning down their previous offer.
The revelations in the phone call set off an argument between the two brothers; Ernie is furious that Lars rejected Zeppco’s offer without talking to him about it (nevermind that he’d almost certainly have pushed his brother to sell, which Lars would never have wanted), while Lars is furious that Ernie tried to sell the factory behind his back. Other issues are then brought to the forefront; Lars claims that he wanted a life outside of string and the factory - implying he was only ever a dutiful son for their father’s sake - but Ernie replies that Lars was nevertheless Rudolf’s favorite child due to playing along with his string obsession, while he was left to be The Unfavorite no matter what he did.
Lars however accuses Ernie of trying to blame others for his own failings; his claim that Ernie can’t cook leads to the argument escalating, and Ernie throwing an orange at him. Lars dodges…and the mouse is inadvertently hit instead, knocking it out. Despite everything, the brothers can’t bring themselves to kill the currently helpless creature, so they instead mail it to Fidel Castro.
The renovation is completed, and the evening of the auction arrives, with Falko, April, Hilde and Ingrid among the guests in attendance. While heading outside to get some fresh air, Lars discovers - much to his horror - that the package containing the mouse has been returned by the Cuban authorities due to insufficient postage, and the mouse has managed to chew its way out. Ernie discovers the mouse for himself moments later, and the brothers throw the auction into chaos as they attempt to catch it once again, with Hilde’s hair being set on fire, and Falko and then April nearly choking on an olive.
In the end, the brothers attempt to flush out the mouse with a garden hose, but flood an inner wall with water after Lars accidentally breaks the tap being used. Falko enters in a bid of $25 million, but before the sale can be made, the water pressure destroys the wall and washes everyone out onto the mansion’s front lawn. Ernie tries to play this off as a demonstration of the mansion’s durability, but it collapses right after he declares “this house will last forever!”. The auction goers leave - April running off with a wealthy Texan - but the brothers take comfort in the fact that the mouse at least appears to be dead now. Unknown to them however, it’s very much alive.
The brothers despondently return to the factory, now the only thing they have left. The mouse stows away on their car’s undercarriage, and after seeing them sleeping in Rudolf’s office, feeds a wedge of cheese into the machinery. The brothers are awoken by the sound of the machinery operating, and find a wheel of string cheese waiting at the end of the production line, with the mouse nearby.
Inspired by this, the brothers renovate the factory to produce string cheese, with Lars managing and Ernie contributing his culinary knowledge, the two brothers working together to run their father's factory just as Rudolf wanted. Lars starts dating Hilde, while Ernie employs the mouse - now on good terms with the brothers - as a taste tester, while also considering plans to make it their mascot/spokesperson. Rudolf smiles from within his painting, before the film ends with a shot of his lucky string (the last thing he gave the brothers before he passed) framed, with a plaque underneath it saying his motto: "A world without string is chaos".
