The Simpsons' dog, Santa's Little Helper, seems to be getting a little too frisky for the family's comfort, and all attempts to tire him out fail. Santa's Little Helper runs off with the family in pursuit. They follow him to the dog-track and find him pursuing a female greyhound racer, named She's the Fastest. The two quickly fall in love and the dog's owner gives her to the family, noting that once a dog falls in love, they lose their "racing spirit".
Santa's Little Helper and his "girlfriend" share various romantic experiences and one day, to the surprise of the family, she gives birth to 25 puppies. The puppies seem to be very cute and cuddly, but are also very troublesome to the entire family: savaging all of Bart's socks (making him wear Lisa's socks, and culottes to "coordinate"), stealing Homer's snacks, and (apparently) soiling the floor nonstop. Homer and Marge decide find new homes for the puppies, much to the dismay of Bart and Lisa. They convince Marge to give the puppies one more chance, but at the end of a near-perfect dinner party, the puppies pop out of the turkey, horrifying and disgusting the all of the guests.
The next day, The family sets out to find homes for the puppies. However, the puppies don't like to be separated. Marge wonders how they will find someone who is able to care for 25 puppies when, Mr. Burns arrives and offers to let them live in his mansion. The family question his motives, but as they do so Burns and Smithers steal the dogs (while the family's back is turned).
Bart and Lisa manage to track the puppies to Burns' Mansion where they spy on him through a window. He seems to be treating the puppies well, giving them a bath as Bart and Lisa arrive. He even picks a puppy who can stand on his hind legs as his favorite, a feat which somehow reminds him of actor Rory Calhoun, and names him "Little Monty". Just as Bart and Lisa think they might have been wrong about Burns, he walks into the next room and loads a gun, preparing to kill the puppies to make a tuxedo out of them.
Bart and Lisa sneak in the window and attempt to escape with the puppies down the laundry chute by tossing Bart's socks down and letting the puppies follow. However, Burns is waiting for them at the bottom (how he got there before them is not explained). As Burns is about to kill the dogs, Bart grabs Little Monty from Burns' hands and places him with the other pups, hoping that Burns won't kill the dogs if he can't tell which is Little Monty. However, Burns tells him to stand up and he does. As Burns bends down to pick up Little Monty, Bart sees Mr. Burns' socks on a clothesline. As he reels the socks above the dogs, they see the socks and all of them stand up. Burns can't tell which is Little Monty, so he prepares to shoot them all. But the standing dogs are too cute for him to kill. He decides to kill Bart and Lisa instead, but cannot kill them either as they are standing on their hind legs "like a couple of little Rory Calhouns". Emotionally touched, he resigns himself never again to wear fur or to kill another animal ("...that can do an amusing trick"). He buys them all and raises them as racing dogs. Later, it is learned that the 25 greyhounds all became world champions, winning millions of dollars in winnings for Burns. The episode ends with Marge reacting to a shadow of what looks like Homer hanging himself over the loss of the dogs in the basement, but Homer is actually batting a light bulb in anger until it smacks him in the head and explodes.