Regina is a mean, hateful woman sought out a large sum of money ($50,000) from her soon-to-be ex-husband, Brillo, and took Missy, a female St Bernard. Though she hated all living things, she planned on giving her back to Brillo once she received the money.

However, Beethoven follows her car and helps Missy escape from Regina's condominium. They "date" and he and Missy have a litter of 4 puppies. The janitor of Regina's condominium found Missy and Regina retook her, and wanted to dispose of the puppies, but the janitor told her she could sell them and make a lot of money.

However, the three Newton children, who owned Beethoven, took it upon themselves to rescue the puppies and kept them safe at their home while hiding them from their father. He eventually found out about the puppies, and tried to convince his wife and children that they couldn't afford them.

Later in the film, Regina, now accompanied by her new boyfriend, Floyd attends the same fair at the mountains as the Newtons happen to be at and manages to steal back the puppies. However, Missy, alongside Beethoven, manages to escape into the wilderness not far from the fair and Regina and Floyd pursue - followed by the Newtons.

When the Newtons catch up with the pair Floyd threatens to toss the puppy he's holding off a cliff and George tells him that things don't need to get ugly - at which point Floyd threatens George with physical violence, prompting Beethoven to ram into Floyd's crotch, causing him to lose balance as he falls off the cliff, Regina grabs his hand and ends up falling alongside him.

Amazingly, the pair survived the fall, landing in a pool of mud - which proceeded to break off, sweeping the two of them into the river as they argue over their plan (as a result, Regina changes her mind and yells at the Newtons: "Take your stinking puppies and stuff it!").

Later, it is revealed that Brillo went to court and Regina lost her claim, gaining none of the money she had sought. Regina and Floyd are arrested, and Brillo was able to keep Missy.