Brain is first seen when he wakes up John Brown from his sleep after dreaming of becoming a police officer. Then he is seen when Penny visits her uncle in the hospital after an accident he had pursuing Sanford Scolex. Brain licks his mouth but Penny tells him not to. Brain is later shown in the Gadgetmobile cruising Riverton with his owners and then taken to the dump after finding out Gadget is there. He goes with Penny to Scolex's (now Dr. Claw) building to find proof her uncle is innocent. While Penny looks for the foot, Brain chases after Dr. Claw, but only manages to pull out his boxers. He is not seen again after this.
In the original TV series, Brain was an intelligent dog who assisted Penny in her missions to foil Dr. Claw's schemes, and often went in disguise to help Inspector Gadget defeat him. However, it isn't until a post-credits scene in the first film where Brain reveals his keen intelligence and talks to Penny through the collar communicator (wristwatch in the cartoon).
In the credits, he speaks with the voice of Don Adams, who was also the voice of Inspector Gadget in the TV series.