A young, interracial couple is among the hostage victims of a diner robbery. Jeremy bludgeons one robber's head with a napkin dispenser and smashes the other's head into the floor. His wife Tracy gasps for air. Her throat is swelling shut.
At the hospital, Cameron notes that the woman has Anaphylaxsis-like throat swelling. House is more interested in the fact that Jeremy and Tracy got married at age twenty. Cameron reports that the woman is not suffering an allergic reaction, but House is again distracted by Wilson chatting animatedly with an attractive new nurse.
House summons a laparotomy for the patient, but one was already performed and it was clean. Noticing marijuana in Tracy's tox screen, Chase theorizes about salmonella from the pot. Foreman calls it a stretch. Without a better idea, House goes ahead and orders floroquinolone for the salmonella.
House attends to clinic rounds and encounters a patient named Michael Tritter who has a rash on his genitals. House quickly writes off the dryness as being a symptom of Tritter's nicotine gum. Tritter asks for a swab to be tested, but House moves on. As House goes to leave the exam room, Tritter kicks out the cane and House trips. Tritter coldly mentions that when you treat people like a jerk, you get treated like a jerk in return. House agrees to take a swab and has Tritter bend over with his pants down. Yet House inserts a thermometer in Tritter's rectum, claiming that he's checking for fever. House walks out, leaving Tritter standing prone in the room.
Foreman visits Tracy to administer the floroquinolone. He inquires about the couple's drug use and is met with hostility from Jeremy. Tracy starts to have an allergic reaction to the antibiotics. Foreman relays this information to House, who realizes that the salmonella was a stretch as Foreman had predicted. House changes his thinking to exercise-based anaphylaxis, figuring that adrenaline from the robbery pushed Tracy's heart rate to the limit.
House puts Tracy on a treadmill to re-enact the stress level of the robbery. Seeing his wife struggling, Jeremy begins to get irritated and jumpy. He clutches his stomach and chest in pain. Jeremy is put in a hospital bed next to Tracy.
Talking through the case, House leads his team into the locker room and breaks into the new nurse's locker, looking for evidence of a relationship with Wilson. He finds a flyer for a jazz festival, but nothing else related to music. Foreman thinks this is ridiculous. House bets him $100 that the nurse is dating Wilson. Much more interested in their latest case, Cameron points out that Jeremy and Tracy either caught the disease from each other or they were subjected to it in the same place. House orders an environmental check.
While searching the couple's tiny studio apartment, Chase finds a box of condoms in Jeremy's jacket. Foreman, knowing what House's reaction will be, wants to ignore it. Chase insists on bringing it back to the hospital. House calls for a genital swab on each patient. Tracy reveals that she already knows about the condoms. They had a recent pregnancy scare and were being extra cautious.
Although the STD tests are clean, Tracy's abdominal pain is getting worse. House orders her removed from the steroids. If she gets a fever, then it is an infection. If not, the problem is environmental. Tracy hallucinates that Jeremy's father is in their room demanding that his son leave her. She screams and Foreman rushes into the room. He can see in her eye that fluid is leaking from the blood vessels in her brain, causing tissue to swell. Tracy lapses into a coma.
The team examines Tracy's MRI and notice aberrations all over her brain stem. Comparing this to Jeremy's chest x-ray, House wonders about sarcoidosis. The team is unconvinced, so House decides to consult Wilson, a sarcoidosis specialist. Wilson disagrees with House's assessment, but House reports back to the team that Wilson said it was sarcoidosis. He orders methotrexate as treatment and a biopsy to be sure of his theory. This stops the team. They know a biopsy on the brain stem is likely to cause brain damage. House is ready to press ahead.
Cameron informs Cuddy about what's happening. She refuses to let House near Jeremy because he will walk all over him. House asks whether Wilson can perform the biopsy on his behalf and Cuddy agrees. Wilson presents the options to Jeremy, but Jeremy would rather have the procedure performed on him instead since they share the same disease. Wilson points out that Tracy could die before his symptoms present. Jeremy won't change his mind. He asks them to stop treating him so that his symptoms come out.
House is frustrated and hides in an empty patient room. The doctors follow, nervous about what he's up to. House wants to inject Jeremy with naloxone in order to subject him to intense pain so that he will relent on the biopsy. The team wants to stop him and he reluctantly hands over the vial. After House leaves, the doctors realize he handed them a different vial. Foreman rushes to Jeremy's room and finds House injecting the naloxone. Jeremy writhes in pain. House badgers Jeremy to consent to the test on Tracy, but he still refuses. The pain only seems to strengthen his resolve because he thinks his symptoms are getting worse and now he is closer to his own biopsy.
Cuddy pulls House into her office where Michael Tritter is waiting for him. Tritter wants an apology, although he's really looking for humiliation. He wants House to think twice about his actions in the future. House refuses.
Jeremy's state has become worse. However, it's not in his brain and he doesn't have sarcoidosis. His intestines are rotting. Both Jeremy's and Tracy's conditions continue to deteriorate. Chase figures Jeremy for ischemic bowel, which means they'll need to remove a few feet of intestine. Foreman thinks that Jeremy likely has small cell vasculitis and Tracy has porphyria, which means their diseases may not be environmental or infectious. It may just be a coincidence. House orders hematin to treat Tracy's porphyria and the removal of Jeremy's dead bowel for a biopsy.
Foreman makes a shocking discovery in the biopsy. Jeremy's bowel isn't dead. The elevated lactic acid levels in Jeremy's stomach leave no other option. But when House looks at the microscope himself, he realizes that Foreman is correct. The bowel is basically fine. House asks the team to go back to the very beginning of their diagnostic process. Jeremy and Tracy grew up next door to each other and ran off to get married after Jeremy's racist, drug-addled father beat him up. House wonders whether it was really racism over Tracy's color or whether Jeremy's dad just didn't like this particular girl. House thinks about Tracy's eyes. They're green.
House realizes that each of the patients has hereditary angioedema. Defective DNA is keeping them from making a critical protein. Jeremy's father must have had an affair with the neighbor that produced Tracy. House orders his team to start treating them for the disease. This brings Tracy out of her coma.
After House's hunch pays off, he wonders who will tell the couple the truth. Foreman thinks they should alert them to the genetic disease but keep their lineage a secret. House wants him to inform the patients or else he will do it himself.
Foreman prescribes Tracy and Jeremy daily pills which will stabilize them because angioedema is treatable. They ask Foreman how they both caught the disease, and he is forced to tell them that it is genetic. Neither of them catches on, so he explains that the hospital has concluded that they have the same father. Tracy gets sick to her stomach. She is lighter-skinned than her parents and people always mention that she and Jeremy have the same eyes.
Later that night, Chase asks Foreman to cover for a few hours over the weekend. Foreman replies that he is going out of town. House realizes that Foreman is the one dating the new nurse. House grumbles that it isn't fair to bet when you already know the outcome, but he still forks over the money.
House speeds home on his motorcycle that night and he's pulled over by police officer Michael Tritter. House scoffs at the idea of a ticket. Tritter, however, noted that he witnessed House pop a pill while examining him earlier in the day. Tritter deems House belligerent and under the influence of a narcotic. He reaches into House's jacket and pulls out of handful of Vicodin. Tritter asks to see a prescription for the drug. When House doesn't produce one, Tritter arrests him for possession.