Steve Martin plays Dr Michael Hfuhruhurr (pronounced Hfuhruhurr), the world's most brilliant brain surgeon and inventor of screw top, zip lock brain surgery. On the rebound from his first wife's death, Michael marries cold-hearted Dolores Benedict (Kathleen Turner), who delights in keeping him at arm's length. On a trip to Austria Dr Hfuhruhurr meets Dr Necessiter (David Warner), a fellow brain surgeon who keeps living brains in his laboratory. Dr Hfuhruhurr discovers his wife is having an affair and on the rebound happens to fall in love with Brain 21 (voiced by Sissy Spacek), from Dr Necessiter's lab and with whom he relates telepathically. On discovering that Brain 21 is deteriorating and needs to be transplanted he needs to find a willing (or not so willing) body soon.