Drama critic Mortimer Brewster (Cary Grant
), despite being also the acclaimed author of The Bachelors Bible
(and Marriage, a Fraud and a Failure,
and Mind over Matrimony
) has finally agreed to marry his sweetheart, Elaine Harper (Priscilla Lane
). Elaine and her father, the Rev. Dr. Harper (Grant Mitchell
), live across the graveyard from the house in Brooklyn where Mortimer grew up. Before going on honeymoon to Niagara Falls, Mortimer and Elaine take a taxi to the old Brewster house, now occupied only by Mortimer's two maiden aunts, Aunt Abby (Josephine Hull
) and Aunt Martha (Jean Adair
), and by Mortimer's younger brother Teddy (John Alexander
), to tell them the news.
Before the happy couple arrives, Aunt Abby is entertaining the Rev. Harper to tea whilst Teddy plays the piano. Police Sergeant Brophy (Edward McNamara
) and Officer O'Hara (Jack Carson
), to whom Brophy is handing over his beat, call at the house to collect repaired toys for a charity. It becomes apparent that Teddy is delusional, believing he is President Theodore 'Teddy' Roosevelt, a condition all regard as a harmless eccentricity -- apart from his habit of blowing his bugle, which disturbs the neighbors. Arrangements have been made by Mortimer for Teddy to enter Happydale Sanatorium once the aunts have passed on.
Aunt Martha comes home, the Rev. Harper leaves, and there are mysterious references to Teddy having "to dig a new lock for the Panama Canal" and "looking in the window seat." Before this is explained, Mortimer and Elaine arrive with their news -- Elaine goes to her father's house -- and there is also a reference to Mortimer's other brother, Jonathan (Raymond Massey
). Left alone for a few minutes, Mortimer pokes around and finds a fresh corpse in the window seat. He immediately suspects Teddy is responsible, and confronts his aunts with this. "But there's a body in the window seat!" "Yes, dear, we know." It turns out the body is Mr. Adam Hoskins, who has been killed using poisoned elderberry wine (made with elderberries from the graveyard and tinctured with a cocktail of poisons from their father's laboratory). Aunt Abby and Aunt Martha have been poisoning lonely old men to help them find peace. Mr. Hoskins is their twelfth, the first being a Mr. Midgeley who died of a heart attack. Teddy buries the victims in the cellar in the "locks of Panama."
Mortimer is, understandably, rather concerned, and is too distracted to talk to Elaine when she tries to attract his attention. He loves his aunts and does not want the police involved, so he determines that Teddy, known to be a lunatic, should take the blame if the murders ever come to light; he thus has to immediately commit Teddy to Happydale. Commitment requires that papers be signed by Judge Cullman (Vaughan Glaser
), Dr. Gilchrist (Chester Clute
), and Teddy. As Mortimer tries to contact Happydale, a Mr. Gibbs (Edward McWade
) arrives to look for a room to rent: he is almost poisoned by the aunts, but Mortimer snatches the wine away just in time. Much to the aunts' disappointment, Mortimer chases Mr. Gibbs away, telling them "This is developing into a very bad habit!"
Mortimer manages to talk to Mr. Witherspoon (Edward Everett Horton
), manager of Happydale, on the telephone, and then rushes out to see Judge Cullman, admonishing the aunts to let no-one into the house before he returns. However, when Mortimer's brother Jonathan and his companion, plastic surgeon Dr. Einstein (Peter Lorre
) arrive, the aunts can't prevent them from entering. Jonathan looks like Boris Karloff as a result of Dr. Einstein's work, and so is not immediately recognized by the aunts, but he convinces them of his identity by remembering details of family history. Jonathan needs another new face, as the police are after him for the murder of one Mr. Spinalzo, whose corpse is in Jonathan's car.
Mortimer manages to get Judge Cullman to sign the papers. At the house, Teddy shows Dr. Einstein the "Panama Canal," where Einstein spots the useful unfilled grave, while Jonathan intimidates his aunts into letting him and Dr. Einstein stay. Jonathan decides to move the car round to the side of the house so he can bring Mr. Spinalzo's corpse in surreptitiously; simultaneously the aunts instruct Teddy to move the corpse of Mr. Hoskins from the window seat down to the cellar. Jonathan, Dr. Einstein and the aunts then 'go to bed,' all intending to be active later, Jonathan and Dr. Einstein to move Mr. Spinalzo, the aunts to hold funeral services for Mr. Hoskins. As soon as the house is dark, Teddy moves Mr. Hoskins down to the cellar, and then Jonathan passes Mr. Spinalzo through the window to Dr. Einstein, who manages to hide the corpse in the window seat before Elaine knocks and enters. She reacts when she learns who Jonathan is; he, suspicious she has seen him with the corpse and the car, tries to shut her in the cellar. The aunts, now dressed in mourning, are roused, and Mortimer returns. He promptly quarrels with Jonathan and once again neglects Elaine, who storms out as he calls Mr. Witherspoon.
Mortimer looks again in the window seat to find a new corpse: "Ye gods, there's another one!" Aunt Abby, confronted, reacts indignantly to Mortimer's suggestion that this is one of her victims, and fetches Aunt Martha to look. When Mortimer and Jonathan both try to stop her, Mortimer realizes that Jonathan is responsible for this latest body. Mortimer offers Jonathan a chance to leave and take the evidence with him, and then Officer O'Hara arrives, wanting to tell Mortimer about a play he's writing. Mortimer gives Jonathan an ultimatum to leave. Jonathan decides not to, and Dr. Einstein discovers Mr. Hoskins' body in the cellar, which they think is Mortimer's work. Mortimer, however, wishes to cut no deal with Jonathan, and rushes out to get the signature of Dr. Gilchrist for Teddy's commitment papers.
Aunt Abby and Aunt Martha come in, and to Jonathan's surprise, admit responsibility for Mr. Hoskins and their other victims. It turns out the aunts and Jonathan have each committed twelve murders, which Dr. Einstein finds hilarious -- he and Jonathan have traveled the world to achieve what the aunts have done staying at home in Brooklyn. As the aunts go down to hold services for Mr. Hoskins, Jonathan decides he needs 'one more' victim -- who will be his hated brother Mortimer. He moves Mr. Spinalzo to Panama and buries him with Mr. Hoskins, much to the aunts' indignation. Mortimer brings Dr. Gilchrist to the graveyard and brings Teddy out to meet him. Teddy greets Gilchrist as "Dr. Livingstone" -- "he presumes." Mortimer then sees Elaine and tells her their marriage must be called off as "insanity runs in my family -- it practically gallops!" Dr. Gilchrist, having just been appointed Ambassador to Bolivia by Teddy, signs the papers for his commitment. Jonathan plots Mortimer's murder with Dr. Einstein by 'the Melbourne method' -- two hours of torture.
Mortimer persuades Teddy to sign the committal papers. Dr. Einstein tries to convince Mortimer to flee, but Mortimer is not listening; in a discussion about the idiocy of victims in plays he allows himself to be overpowered, gagged and tied up. Jonathan prepares to set to work on the Melbourne method. Dr. Einstein, distraught, needs a drink, and seizes the decanter of poisoned wine, pouring himself and Jonathan each a glass; as they are about to drink, Teddy startles them by blowing his bugle and they drop their glasses. Jonathan, realizing the neighborhood will be roused, decides on murder the quick way, but Officer O'Hara arrives and sees Mortimer tied up. Dr. Einstein persuades him that Mortimer is enacting a scene from a play. O'Hara refuses to untie Mortimer, and instead (with a captive audience) recounts the plot of the play he is writing. Jonathan tries to kill O'Hara, but is knocked out by Dr. Einstein using a shoe. Sergeant Brophy and another policeman, Officer Saunders (John Ridgely
), arrive and telephone back to the station "calling off the big manhunt." The manhunt is for O'Hara, who has not called in, but Jonathan believes they're talking about him and gives himself up. Then he reacts violently to the suggestion that he looks "like Boris Karloff."
In the resulting fight Mortimer frees himself. Lieutenant Rooney (James Gleason
) arrives and recognizes Jonathan as an escapee from the Indiana Prison for the Criminally Insane. Teddy's President Roosevelt act confuses the Lieutenant, but Mortimer assures him that Teddy is due to go to Happydale, and that Teddy's tales of "thirteen bodies in the cellar" are part of his delusion. However, Teddy has to be persuaded to re-sign the commitment papers as Teddy Brewster rather than Teddy Roosevelt. Mr. Witherspoon arrives to collect Teddy (to go "on his hunting trip to Africa"). Elaine sneaks into the house through the cellar.
Aunt Abby and Aunt Martha, distraught about being separated from Teddy, want to commit themselves to Happydale too. Mr. Witherspoon is reluctant, as he thinks they are sane, but when they also start talking about the "thirteen bodies in the cellar," he agrees. Needing a doctor's signature, they rope in Dr. Einstein. Einstein then escapes even though his wanted description is telephoned through in his hearing and that of the Lieutenant. Mortimer signs as next of kin, which worries the aunts. They reveal that he is in fact not a Brewster; his father was a chef on a tramp steamer and his mother was a cook whom the aunt's brother married. Mortimer is delighted ("I'm the son of a sea-cook!") that he isn't a biological member of the homicidally insane Brewster family, and so can marry Elaine without fear that he will go mad and breed mad children. Elaine emerges from the cellar, having discovered the graves, and has to be kissed by an ecstatic Mortimer into forgetting this. The movie ends as he picks her up and runs away, much to the amazement of the taxicab driver (Garry Owen
), who has been waiting for them throughout.