Mental patient John Burns (Akyroyd) gets the chance to fill in for his doctor when he intercepts a telephone call while being reprimanded in the doctor's office, asking if Dr. Baird could fill in for Dr. George Maitlin (Grodin) on his popular radio talk show. Burns jumps at the chance to escape the mental hospital, and with the help of Dr. Baird's secretary manages to break out and get to the airport to pick up a waiting ticket, assuming Dr. Baird's identity in the process.
When Burns arrives in L.A. he is met by Dr. Maitlin's radio show assistant Laura Rollins (Dixon) and escorted to the waiting limousine where he crosses paths with Donald Becker (Matthau) a crazy priest who is collecting money to save plants, Becker recognises the trousers Burns is wearing to be asylum issue and ends up riding the gravy train with him. When the time comes to do the radio talk show Burns is a huge hit, offering people free consultations and using profanity on the air, he even arranges for everyone who comes down to the radio station to go to a ball game for free (where he also leads the singing of the national anthem).
All goes well until Dr. Maitlin meets the real Dr. Baird in London when they both attend the same seminar, they realise something is wrong and fly back to L.A. to try and find what is going on, meanwhile Burns has been given his payment for the show (in cash) and is ready to leave by aeroplane when he sees on the in-flight TV that Becker is on top of the Hollywood sign shouting Baird's name. Burns decides to go back and help to resolve the situation where he is arrested only to be rescued on the way to the penitentiary by Becker and Maitlin's assistant Rollins.
In the last few scenes of the movie, Burns gives his inmate number "7474505B" which is the same number that Jake Blues had in the The Blues Brothers (film) and Louis Winthorpe III in Trading Places.