Brain comes face to face with his former friend and now enemy, Snowball. And it seems Snowball has his own plans to take over the world.

Animal rights activist think Pink and the Brain are monkeys and release them into the jungle after taking them out of Acme Labs. The pair try to make it back home, but run into the Brain's old enemy Snowball.

Pinky and Brain are kidnapped in Washington, DC by an unknown force. Brain loses his memory and the mice are then imprisoned in a town where everyone is forced to perform the Schëerskåhøvên, which is dumbing down the entire country.

Brain regains his memory and the mice escape. They believe Snowball is responsible for the Schmëerskåhøvên, but him imprisoned in a mental institution.

The mice and Snowball search for the one who spliced their DNA, Dr. Mordough, thinking he's responsible for all this. But it turns out to be his cat, Precious, and time is running out.