Lab scientists subject The Brain to experiments testing the addictive properties of cigarettes, an experience that endangers his latest plan for world domination.
The Brain gets wild and crazy on a night when he and Pinky don't try to take over the world. The Brain tries to infiltrate a group of surfing teenagers in this spoof of beach party movies.
When studio executive Sandy Dreckman presses them for higher ratings, Pinky and the Brain try out different ideas for their show, spoofing various other sitcoms; and quit over creative differences as their careers gradually decline.
During a White House conference on the topic "the brain," one of the president's assistants mistakenly invites The Brain. After he becomes trapped in a web of conspiracy and deception, The Brain gets brainwashed and Pinky must save him.
The Brain and Pinky escape from the land of Hats, but find someone is still after them as they try to save the world from an evil dance, the Schmeerskahoven.
To facilitate The Brain's latest plan, he and Pinky ship themselves to Russia, where they become involved in a James Bond-style adventure. Pinky and The Brain find themselves trapped in the familiar nursery rhyme.