The cartoon begins with Homer and Marge Simpson driving away from a pet store in their van. At that moment, Dingo and Pup go into the pet store to buy a pet. Dingo sees and falls in love with a cute puppy named Whistle, while Pup has his heart set on a vicious dog that is locked up in a steel cage. Dingo denies Pup's wishes, but Pup soon grows to like Whistle as much as Dingo when the puppy gives him an affectionate lick.
Elsewhere, Comic Book Guy, an animal catcher, is contacted via radio in his truck to attend to an urgent issue. As Comic Book Guy arrives at the scene, he finds a hysterical Pouches covered in purple bruises. Pouches explains to Comic Book Guy what happened and then runs away in fear. Comic Book Guy opens the door to a nearby house, when suddenly, tentacles pop out the door and windows of the house. He looks in to see a giant squid clutching Slap, Tara The Android, Pancake, and Kid in its grasp. The tentacle holding Pancake repeatedly slams her onto the floor, killing her. Comic Book Guy readies a mouse trap, enters the house, and single-handedly disables the squid, dragging it behind him to his truck, with Pancake and Tara still in its tentacles.
At Dingo's house, Pup happily plays with Whistle in his bedroom. Dingo leaves the room, whistling as he goes, but returns to the room upon hearing Pup screaming. He enters the room to find blood everywhere, furniture destroyed and Whistle attacking Pup. As Comic Book Guy finishes tying the squid to the back of his truck, he gets a call from Dingo, himself now being attacked by Whistle, asking him to come help. Comic Book Guy arrives and sees Dingo carefully dangling Whistle on a leash, trying to make him calm down. Comic Book Guy slowly puts his net under Whistle and picks him up, and walks away. But before Comic Book Guy gets the chance to put him in a cage, it is revealed that Whistle has escaped by chewing through his net.
Meanwhile, at his hole, Bugs Bunny puts a tea kettle on his stove and takes a basket of laundry outside. As he begins hanging his laundry on a clothes line, Whistle approaches. Bugs says to him with his trademark catchphrase "Eh, what's up, doc?". But then, Whistle begins viciously attacking Bugs by biting on his buttocks, ripping the skin off and exposing the nerves. He shrieks as Whistle continues biting the skin off his butt. Bugs attempts to flee, screaming. Comic Book Guy hears Bugs Bunny's screams of distress and rushes to his aid. Meanwhile, Bugs is shrieking while holding onto a tree branch as Whistle continues biting on the skin of his butt, holding on. As his wrists peel, Bugs escapes by jumping into a washtub filled with water. Comic Book Guy arrives to see the half-skinned Bugs Bunny running off.
Comic Book Guy is confused and thinks about the situation when Bugs Bunny's tea kettle begins to whistle. Whistle suddenly gets aggressive and begins biting Comic Book Guy's chest. Comic Book Guy pulls Whistle off him and throws Whistle into the streets near Lumpy. Lumpy sees Senior driving down the road, about to hit Whistle. As Comic Book Guy hops over a fence, Lumpy blows on a whistle to warn Senior, causing Whistle to grow aggressive and attack Senior in his car. Senior's car swerves near Laurence McDinglehooper, who is strutting down the sidewalk. Lumpy blows his whistle again to warn Laurence of the approaching vehicle, but this only causes Whistle to start attacking Laurence.
Comic Book Guy begins thinking about the connection between Whistle's attacks, slowly connecting the dots in his head. By now, Whistle has begun tearing out Laurence's intestines and runs away with them as Laurence falls dead. Lumpy once more blows his whistle, causing Whistle to turn his sights on Lumpy. Comic Book Guy has finally figured out that whistles are what trigger Whistle's aggression, and he tackles Lumpy just as Whistle is about to attack him. While Comic Book Guy accidentally swallows the whistle, Lumpy is knocked halfway into the road, where his head is run over by a passing car.
As Comic Book Guy struggles to breathe with the whistle in his throat, he lets out whistling noises, which cause Whistle to chase after him. Comic Book Guy is brutally attacked by Whistle, but is able to escape and hide. He successfully coughs up the whistle, but when he lets out a whistle of relief, Whistle appears and chases Comic Book Guy up a tree. Whistle then attempts to climb up the tree, repeatedly scraping the wood away. Later that day, during night, now with half of the tree stump scraped away, Whistle has snapped out of his feral state and fallen asleep. Comic Book Guy picks up the sleeping Whistle. But as Comic Book Guy begins walking back to his truck, it is revealed that the squid he caught has regained consciousness, and is now standing on its tentacles.
Down the road, Homer and Marge are seen fighting over a dollar in their van. This distracts them until they realize that they are driving towards the squid. As the two Simpsons begin screaming, the squid releases ink onto their van. Unable to see through the ink-covered windshield, they activate the windshield wipers, but it is not enough to wipe off the ink. As a result, Homer and Marge crash into a tree close to the one Comic Book Guy was hiding in. They slam onto the tree with so much force, they fly right through their windshield and get crushed like soda cans when they fly into the tree at high speed.
The back of their van opens up and dozens of dogs identical to Whistle fall out of the back, knocking Whistle out of Comic Book Guy's hands. Not knowing which is the real Whistle, Comic Book Guy connects the dots in his head again, grabs Lumpy's whistle, and blows it. One of the dogs arches its back and snarls, leading Comic Book Guy to believe he has found the right one, when suddenly all of the other dogs do likewise. The dogs then jump onto Comic Book Guy and begin to maul him to death.
The final scene shows all the dogs back in their normal state, except for two, who are seen fighting over Comic Book Guy's severed mustache, the only thing that remains of him.