- In a zany parody of hospital soap operas, a new batch of doctors begins their internship at City Hospital.
- An 'Airplane'-style spoof of hospital soap operas: a brilliant young trainee can't stand the sight of blood; a doctor romances the head nurse in order to get the key to the drugs cabinet; there's a mafioso on the loose disguised as a woman - in other words all the usual ingredients present and correct, though in this case the laughs are intentional.—Michael Brooke <michael@everyman.demon.co.uk>
- Beginning their one-year residency to become doctors, a group of young medical interns - psychiatrist Dr. Walter Rist (Patrick Collins), gynecologist Dr. Thurman Flicker (Rick Overton), anesthesiologist Dr. Charles Litto (Kyle T. Heffner), pediatrician Dr. Milton Chamberlain (Gary Friedkin), sports medicine Dr. Bucky DeVol (Ted McGinley), and overtired, student loan debt-ridden allergist Dr. Phil Burns (Taylor Negron) - introduce themselves to the intimidating City Hospital administrator, Dr. Joseph Prang (Dabney Coleman). Also among the students are the virtuous Dr. Stephanie Brody (Sean Young) from a small town in Vermont, and the arrogant yet determined Dr. Simon August (Michael McKean) from Beverly Hills, California, who intends to become "the greatest surgeon the world has ever known." When reporting for their first shift just after midnight on New Year's Day, they find the lobby and emergency room areas in a state of chaos.
Meanwhile, organized crime lord Salvatore "Sal" Bonafetti (Titos Vandis) hides in a safe house with his son, Angelo Bonafetti (Hector Elizondo), to protect himself from rumored assassination attempts by rival Mafia families. When Sal suffers from a stress-induced stroke, Angelo dresses himself and his father in disguises before taking him to the hospital, where they are pursued by an assassin named Malamud (Michael Richards).
While watching Simon curtly diagnose patients, Stephanie instantly disapproves of his insensitive bedside manner.
Later that morning, Malamud finds Sal's room, but the nurses mistake him for a patient and force him into the neighboring bed, worsening Sal's paralyzing anxiety.
During a training lesson, Simon's astuteness enrages their supervisor, Dr. Oliver Wendell Ludwig (Harry Dean Stanton), but impresses Stephanie, who asks him on a date. During dinner that night, Stephanie tells Simon about her hometown community, which funded her medical school education so she could take over her ailing father's practice. Simon discredits her humble background, causing her to become angry. When she stands up to leave, however, she doubles over in fleeting abdominal pain, destroying the restaurant's outdoor patio tent.
At the hospital the next day, the nurses find a patient file belonging to another "Malamud" and erroneously prepare the assassin for surgery to remove one of his kidneys.
While observing a patient, Simon expresses his interest in continuing his relationship with Stephanie, but they agree to remain professional.
After receiving a raunchy prank love letter from someone he believes was the uptight Nurse Norine Sprockett (Pamela Reed), Phil Burns flirts with her in order to gain access to stimulant medications from the locked prescription cabinet.
Angelo continues visiting his father Sal in the hospital while dressed as a woman named "Angela."
On Valentine's Day, Simon runs into Stephanie teaching a community dance class, and confronts her about her suddenly cold attitude toward him, hoping to make amends. When Stephanie once again collapses in pain, Simon tricks her into collecting a saliva sample, which he sends to Dr. Ludwig to run tests for a rare and fatal disease. Impressed with Simon's intelligence and attitude, Dr. Prang invites him to prove his surgical capabilities by performing an appendix removal.
One day, a man code-named "Vanilla" asks to buy medication from Phil, prompting the doctor to continue courting Nurse Sprockett, who has transformed her appearance to make herself more attractive.
Skipping forward several months later in July, Malamud complains about the many unnecessary procedures he has been forced to undergo over his seven month confinement in Sal's room.
The interns watch as Simon begins his surgical test, but the pressure causes him to recall a traumatic experience from childhood, in which his parents played a practical joke on him during a mock "surgery" on a piñata. Overwhelmed by the pressure, Simon runs out of the room and retreats to a nearby cemetery to contemplate his future. Offering to help restore his confidence, Stephanie brings him back to the now-empty surgical theater, where they make love on the operating table.
Dr. Ludwig announces that Stephanie's test results came back "negative," lying about having tested her for the specific disease.
Meanwhile, Angelo's wife becomes concerned by the increasing amount of time he is spending at the hospital with the compassionate Dr. Walter Rist, who is unaware that "Angela" is actually a man.
Another few months later in December near Christmas, Walter invites "Angela" to a holiday party at Dr. Prang's house, where Stephanie announces she is willing to give up her dream of returning to Vermont in order to get married and live with Simon in Beverly Hills. However, Stephanie collapses, and Dr. Ludwig reveals that she really has the condition Simon suspected, which is only curable through dangerous surgery. Dr. Prang is the lone surgeon to ever successfully perform the procedure, but he refuses to do it again until Simon persuades him by punching him in the face.
Having secretly made a copy of Nurse Sprockett's medicine cabinet key, Phil now steals prescriptions at his leisure, but she eventually discovers his deception when he and "Vanilla" are arrested by undercover police officers.
Dr. Prang practices the surgery on a mannequin in order to prepare for Stephanie's operation, but just before the procedure, the hospital nurses go on strike over a wages dispute, and Dr. Prang learns that his recent divorce proceedings have left him bankrupt. Ignoring his summons to the operating room, Dr. Prang chases his accountant at gunpoint throughout the halls of the hospital, forcing Simon to assume responsibility for Stephanie's life. Although he has the assistance of Dr. Ludwig and some of the other interns, Simon believes Stephanie's body has rejected the treatment, and he sulks out of the room. Once gone, the remaining doctors realize that the equipment was unplugged, and Stephanie revives. The interns wheel her on a gurney after Simon, and the two lovers kiss.
After her recovery, Simon and Stephanie get married in the hospital hallway.
When his father is ready to be discharged, Angelo writes Walter a letter stating that, despite the doctor's attraction to "Angela," they cannot be together because he is already married. Walter then begins a relationship with Nurse Sprockett.
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