An older woman at her home, Fran, answers the door and greets Robin, a younger woman working for an "agency." Robin finally quotes her a price of $1,000, satisfaction guaranteed, and when Fran goes to get the money and finds her cat up on the shelf, Robin slips into a slinky dress. Fran starts to get dizzy then collapses and Robin is unable to wake her up. She grabs the money then calls an ambulance.
Wilson examines Fran and Robin is there covering for their activities. Wilson finds a motion-sickness patch and concludes that's responsible. Wilson removes the patch and Fran has a seizure and collapses. Meanwhile, House and Cuddy are getting on a plane after House gives a speech in Malaysia and cranks up a considerable bill at the hospital's expense. He manages to cover it by downgrading Cuddy to Coach.
Wilson questions Fran and determines she went to Caracas recently and had a number of drug and sexual escapades. On the plane, a man next to House starts vomiting and he manages to trick Cuddy into switching places with him.
Wilson goes over Fran's case with House's staff and sends them out to check things out. Cuddy confronts House and they disagree on the diagnosis including the man's rash, and House tries to reassure the stewardess. Chase and Cameron go to Fran's house and after discussing their relationship, Cameron decides to have sex on the bed while the cat looks on.
On the plane, another person starts vomiting and House notices she has the same rash. With Cuddy busy, House rounds up the passengers to stand in for his staff while running a differential diagnosis. They're too far to turn around at this point and Cuddy shows up to eliminate the possibilities. House concludes it's food poisoning from the sea food kabobs and tells the passengers to go to the restrooms to vomit.
The staff turns up nothing on Fran's tests and Wilson figures she has breast cancer. Meanwhile House forces the first victim to get up so he can determine if he has weakness of the joints, which he does.
Wilson confronts Robin and tries to figure out what her relationship to Fran is. He asks her to stand in as Fran's friend and Robin reluctantly agrees. Cameron administers a mammogram as Robin stays for Fran and tries to reassure her that she didn't do anything stupid. Fran complains of blindness in her right eye.
House now believes that radiation sickness is responsible and the second victim is pregnant and her symptoms are similar but not from the same source. However Cuddy interrupts him to point out he's wrong… as she starts vomiting and gets a rash.
While Fran undergoes eye tests, House determines Cuddy is photosensitive and she asserts they need medicine before the illness spreads any further. Robin finally leaves but asks Wilson to let her know what happens to Fran. Cameron is discussing her relationship with Chase, with Foreman, when Fran passes out.
House goes through the plane collecting any medicine he can while back at the hospital, the staff disagrees on the diagnosis for Fran until finally Chase agrees with Cameron on her proposed lumbar puncture test but it turns out they're wrong.
House and Cuddy conclude they have to tap into the first victim's spinal cord with a LP despite the fact the airplane isn't stable. House determines that the fluid is clear which supposedly shows bacterial meningitis and informs the passengers to let him know as soon as they show symptoms. They start showing the symptoms he mentions and House announces they're suffering from mass hysteria. He points out that even Cuddy fell victim to the hysteria, but that leaves them with one problem: what is the problem with the first patient, Pang.
It's back to what passes for a white board on the plane and House figure that a condom is responsible: Pang is a drug mule who is smuggling cocaine in his stomach and the condom burst, spreading the cocaine throughout his system and causing his illness. They'll have to operate to save him.
As they take Fran into surgery, Chase wonders if their relationship is compromising their judgment. Then he remembers that the cat's bowl at the house was full.
House prepares to operate while Chase goes back to Fran's house and finds the cat dead. He goes to the basement and finds an open pipe. House prepares to cut Pang open but then the boy helping him presses down, causing an easing of the pain. House figures that pressure on his joints relieves his pain, so checks his wallet.
Wilson and Foreman prepare to drill in to Fran's skull while Chase follows the pipe outside and over to the next house which is being fumigated. He calls Cameron who stops the operation. House goes through Pang's wallet and finds he was scuba diving: he has the bends due to the low pressure from the flight.
The staff explains to Fran that she got a dose of the fumigation poison, and she says that she thought she was being punished.
The plane lands safely and House points out that Cuddy owes him. She denies it and as they leave, the stewardess hits on House. Wilson calls Robin to reassure her… and ask her out. As Cameron and Chase leave, Chase says he wants more and she refuses, saying it's over.