Fran is a seemingly conservative, middle-aged woman. She collects porcelain figurines and wears a cable-knit sweater. Fran welcomes a woman named Robin into her home. Robin is a prostitute. When Fran sees the woman's revealing outfit, she becomes dizzy and faints. Robin calls an ambulance.
As Robin stands nearby, Wilson examines Fran. He finds a motion sickness patch on her neck. Fran assumes that she forgot to take it off after a trip to see her sister in Duluth. Wilson informs her that scopolamine can cause dizziness and blurred vision, and the blackout most likely occurred when she conked her head on the floor. As she is being discharged, Fran falls to the floor in a seizure.
After she is readmitted, Wilson notices a fresh tattoo on Fran's leg. He questions whether she really went to Duluth. Fran confesses that, when she recently turned the same age her mother died at, she decided on a whim to visit Caracas. While there, she got a tattoo, drank, partied and had sex with a stranger.
Wilson presents Chase, Cameron and Foreman with Fran's new case study and a litany of potential diseases. Wilson orders them to get a tox screen, chem 20, STD panel, blood cultures, a CT scan and to also check Fran's house for possible environmental causes.
Meanwhile, House is wheeled onto an airplane in Singapore with Cuddy. His vinter's cane -- which hides a corkscrew -- was confiscated by security. Cuddy laments the incredible room charges House accumulated in a Singapore hotel. He defends himself by explaining that she shouldn't have dragged him across the globe simply for a three-minute speech, even though it acquired Princeton-Plainsboro WHO accreditation.
On the flight, the man across from House seems ill. The man named Peng groans and then vomits on his food. Keo, the flight attendant, asks if anybody speaks Korean or is a doctor. House gets up, and then walks to the back of the plane to get Cuddy.
Cuddy is worried that Peng is suffering from meningococcus. The whole plane could end up infected and she thinks they need to turn around immediately. House, having noticed Peng's medic alert bracelet, passes it off as a mere allergic reaction. Moments later, another passenger named Joy starts to vomit. House figures it was just the smell of Peng's vomit that made her sick. Yet when he lifts up Joy's shirt, he sees that her back is covered with the same nasty rash that plagued Peng. House becomes officially concerned.
House heads to the front of the cabin and begins writing various symptoms on the movie screen as if it was his white board. Cuddy informs House that the plane has passed the halfway mark, and they are now at least six hours from landing. House asks Keo about the dinner menu. Peng had eaten sea bass and Joy had seafood kabobs, which contained sea bass. House declares that they are suffering from ciguatera poisoning, which is an instant-onset toxin claiming all of the symptoms House scribbled on the board. House gets on the PA system and asks everybody who had the sea bass to go into the bathrooms and vomit as soon as possible because it should keep the effects of the toxin to a minimum. Cuddy then whispers to House that meningococcus still makes just as much sense. House admits that she's right.
Peng's health worsens. If they soon start seeing neurological symptoms, they will all be in trouble. Testing for ataxia, House indicates to Peng that he should stand up and walk toward him. Peng's legs lock and he falls to the ground.
House examines Peng's leg and sees that it's thin, probably from a recent break. He declares that Peng has radiation poisoning from the x-rays. He tells Joy that she's pregnant. All of the symptoms fit both diagnoses. Suddenly, Cuddy doubles over and vomits. House finds a fierce rash on her back as well. She didn't even have the fish.
Back in Princeton, the team comes up with negative results for all of Fran's tests. However, her seizures have slowed since the doctors put a motion sickness patch back on. They were concerned the scopolamine was controlling her symptoms. Wilson realizes that she is suffering from breast cancer. Since she was on vacation, he assumed that Fran had an exotic problem. But the inflammation triggered by the paraneoplastic syndrome caused by cancer can be reduced by the anticholinergics found in motion sickness patches.
Cameron performs a mammogram on Fran when she begins blinking. She can't see out of her right eye. The doctors perform a Visual Evoked Response test with a dozen electrical anodes attached to Fran's forehead. Various patterns shine on a screen in front of her.
In the skies at the same time, House shines a flashlight in Cuddy's face. Agitated, she waves the light away, then declares she has photophobia, a symptom of meningitis. Keo comes into the cabin with word that three more passengers are sick. House walks through the cabin with a young patient in an attempt to collect any medications that passengers might be carrying.
In the hospital, Foreman and Cameron note a spike on Fran's EEG in her left eye. She falls into a coma. The team bickers about how to proceed. Foreman insists she has a cranial bleed that the CT missed and that they need to create a burr hole immediately to relieve the pressure. Cameron, doubtful the test would miss it, suggests an LP to confirm the presence of red blood cells. She asks Chase what he thinks and he agrees with her. Foreman rolls his eyes, growing tired of their relationship causing Chase to always agree with Cameron. Wilson decides to play it safe and go with the LP first.
Cameron and Chase prepare Fran for the LP. House is preparing to do the same on Peng, but with much more meager supplies. A syringe with plunger removed, a plastic shot glass and an alcohol swab. The needles are inserted in each patient's back. House collects the liquid that drains out in a shot glass. Chase does the same, only into a sterile test tube.
House hasn't found much in his pill collection, but there are three tablets of augmentin. Cuddy wants them given to Peng because he's in the worst shape, but House reminds her that he's allergic to penicillin. If he has a reaction, he dies and they've wasted the pills. House then realizes that Cuddy is right.
House studies the liquid from Peng's spinal column and his face drops. Ignoring Cuddy's frantic pleas to know what it is, House heads to the main cabin and informs the passengers that they have a confirmed case of bacterial meningitis. Peng will not survive and it's likely that several others have also been infected. Anybody who feels the various symptoms needs to come to the first class cabin for isolation. The passengers start to panic. House warns them that they all don't actually have meningitis, but are merely suffering from mass hysteria.
He pleads for everybody to calm down so that their imagined symptoms will soon disappear. House returns to the first-class cabin and tells Cuddy that the clear LP fluid confirmed his thoughts. Her rage, a symptom of mass hysteria, gave rise to a new theory. However, Peng is still dying and House has absolutely no idea why.
House scribbles new symptoms down on the movie screen and convenes three passengers to play the roles of Foreman, Chase and Cameron and run through the differential with him. Cuddy mentions syphilis. Thinking of condoms makes House realize Peng has focal limb paralysis. Peng may have swallowed cocaine-filled condoms as a courier, and the drug might be spreading through his digestive tract. They need to operate.
In order to perform surgery on Peng, House asks if any passengers snuck a knife on board. A man reluctantly admits that he has a ceramic knife which wasn't sensed by the metal detectors. House's new team helps pin Peng to the floor as he prepares a pair of gloves, three plastic spoons, four alcohol wipes, a small pair of pliers and a sewing kit.
The 12-year old boy assisting House presses down on Peng's shoulder, which seems to relieve the patient's pain. Noticing that pressure on Peng's joints relieves pain, House realizes he's wrong about the cocaine. They need to find Peng's wallet.
House uncovers what he's looking for in the wallet -- a receipt from a scuba rental shop. Peng has the bends. They need the pilot to descend under 5,000 feet as quickly as possible and drop the oxygen masks.
Back in the hospital, Fran is wheeled into surgery with her head shaved. Chase and Cameron watch from another room. He thinks their relationship is actually affecting their work. They even had sex in Fran's bedroom while checking for environmental causes. Cameron mocks Chase for being worried about Fran's cat watching them. This triggers a revelation for Chase. Fran hasn't eaten anything since entering the hospital. He rushes off.
Chase re-inspects Fran's home. The cat is now dead, although its food bowl is still full. The surgery team prepares to drill into Fran's head and Foreman peels back a section of her scalp, exposing the skull. In Fran's driveway, Chase finds a pipe that leads to the house next door. Tacked to the front door of the next house is a notice that the place has been fumigated with methyl bromide. Chase quickly calls the hospital and tells them to stop surgery.
The doctors explain to Fran that fifty years ago, her home was one estate. The two homes shared an electrical system. Unfortunately, the exterminator didn't realize that. When it was fumigated, the poison gas flowed through the electrical conduit into her home. She will need to stay in the hospital for a few more days, but ultimately she'll be fine.
The flight finally touches down in New York. Keo slyly lets House know that she is in New York every Monday.
Wilson calls the prostitute Robin to let her know that Fran will be fine. Then he asks if she might be coming back to visit.
As they leave the hospital that night, Chase tells Cameron that he wants their relationship to be a little more normal. He doesn't want simple sex any more. Cameron reminds him that's what he signed up for originally. If he's no longer game, it's over.