A 10-year old boy named Matty puts on a sterile hospital gown and latex gloves. His mother Claudia does the same. She prepares Matty to see his older brother, Nick, who just went through an extra course of chemo and radiation for leukemia. When he enters the isolation room, Matty is frozen by the sight of his bald brother. Wilson takes Matty off for his own procedure -- a bone marrow donation. As Wilson discusses the importance of the surgery, Matty sneezes. Wilson can't do a transplant until he knows what's wrong with Matty.
The team gathers to discuss the case. Matty has an enlarged spleen and fever. Even if this was just a basic cold, a bone marrow transplant right now would kill Nick. Since the family is black, it is almost impossible to find another donor. House suggests making Matty sicker in order to induce the infection the become more prevalent and easier to spot. Foreman disagrees, figuring they should check the family home for environmental causes.
Foreman and Chase inspect the home. Still shaken by the death of his last patient, Foreman asks Chase for advice on how to move forward after botching a diagnosis. Chase replies that time eventually allows you to stop thinking about it on a daily basis. Foreman argues that Chase was distracted by the death of his father when he accidentally killed a patient, whereas Foreman made a calculated decision. Chase sees a rusted water pump in the backyard and he takes a water sample. Perhaps Matty took a drink one day after playing baseball in the backyard?
Back at the hospital, the doctors question Matty about the fountain. He did drink from it once last summer, but the water was disgusting and he never tasted it again. Matty also suffers from an acute scrotum. House sees this as a positive sign because only a few infections cause swollen testicles. He orders urinalysis and cultures for E. Coli, klebsiella, TB and brucellosis. He also wants blood tests for enteroviruses and adenobviruses.
The tests all come back negative, so Chase begins to wonder if they're on the wrong track. In their quest to make Matty sicker, they might have inadvertently helped the infection spread to his heart. Chase and Cameron perform a transesophogeal echo on Matty and find a growth on the mitral valve. It will require at least a month's worth of antibiotics to clear that up. However, Nick only has about four days to live.
House suggests removing the valve, but Chase doesn't think the infection will clear the boy's system in time. Foreman believes that Matty will be fine with antibiotics and doesn't need open heart surgery. House shifts gears, and decides they can perform the valve surgery. Then they will harvest Matty's marrow, stew it in the targeted antibiotic and replace it. Concerned about this wild plan, Foreman announces that he's going to run it by Cuddy.
After hearing the various arguments, Cuddy orders Wilson to simply explain the choices to the parents. She asks House why he let Foreman go far with his caution. House explains that he thought it would be good for Foreman since he seems to now be frozen in his decision making. He has the yips, much like how a great athlete might suddenly lose his determination. Of course, House only plans on giving Foreman four days before he fires him because one doesn't recover from the yips.
Wilson breaks it down for the family. This procedure should work, but due to the valve replacement, Matty would have to be on blood thinners to prevent clots for the rest of his life. It would prevent him from playing baseball due to the risk of hemorrhage. Wilson advises them to protect the family as a whole and opt for surgery. They consent and the surgery is begun.
That night, Wilson wakes up House. They biopsied a piece of the valve before removal. It was fibrous tissue and not infectious. Now they have to figure out what is turning Matty's healthy heart tissue into gristle. Cameron thinks it could be autoimmune, so House sends them off to figure out which one.
All tests for autoimmunity are negative. What's worse is that Nick is starting to deteriorate. His capillaries are leaking blood. If that moves to the brain, he's dead. Cameron suggests going with the 4 out of 6 level marrow match Foreman found in the registry. House rejects that because he wants a 6 out of 6 level match.
Foreman, however, informs the family about the 4 out of 6 match which gives Nick a chance. The parents are greatly encouraged. House and Wilson later try to talk them out of it, but it's no use because they have made up their mind. Outside, House berates Wilson for not having the courage to manipulate the parents into what the doctors feel is the right decision. At least Foreman was doing what he thinks is right.
The transplant is started on Nick. Foreman hooks up antibiotic IVs to Matty. Later, Cameron checks up on Matty, who complains of an itch. She sees blood dripping from his ear and calls House with the news. Matty's not making new blood cells and his bone marrow is crashing. House thinks they need to stop Matty's meds. If he recovers, then the meds were the problem. If not, it's the infection. Matty is in worse shape than they thought.
House and Wilson return to the hospital and promptly learn that Nick is suffering from a grade four Graft vs. Host issue. The new marrow is killing him. House asks Foreman if he's feeling guilty, but Foreman is adamant that he did the right thing.
Matty isn't improving, meaning that the infection is to blame. House has an epiphany. If blood cells won't grow in Matty because he's too weak, they should put Matty's blood in Nick and see what happens. Maybe that will lead them to the infection in question. Since Nick is going to die anyway, they can use his body as a Petri dish to quickly tell them what the issue is. The doctors don't see any other way.
Wilson presents this situation to the family. At first, they refuse to accept that Nick is as good as dead, but House makes it clear that there's no coming back for him. The only question, as House sees it, is whether they leave the hospital with one dead son or two. With House's prompting, Wilson encourages the parents to consent. Yet they say no. They're not giving up on Nick.
House is stumped. Foreman is ready to start testing Matty to learn what infection he has. House scoffs that with 10,000 possible infections and 20 minutes per test, it'll take Foreman about eight years to pinpoint the cause. Foreman counters that it will actually be four months. Unless, of course, they get lucky and Foreman is right with the first test.
Nick writhes in agony. House writes out a new prescription and gives it to Nick's father, who runs off to get it filled. House intentionally wanted to be alone with Nick. He explains that he is dying, but Nick already knows that. House says that his life doesn't have to be meaningless. He could save Matty.
Meanwhile, Wilson and Foreman churn through tests. Wilson tells Foreman that House is going to fire him because he feels he's gotten timid. Foreman couldn't care less about that right now. He would rather focus on waterborne infections since Matty drank from the old pump. Wilson wonders why a cookie cutter house in the suburbs has an old fashioned hand pump in the yard. Foreman realizes that this is rather odd.
Nick talks with his parents, trying to persuade them to let him go in order to help Matty. He wants to do it for them so that they won't be alone. The parents break down and consent. Before they can wheel Nick away for the procedure, Foreman bursts in with the news that they figured out what's infecting Matty. He's got a fungal infection called histoplasmosis. It's found in chicken feces. The subdivision was built on top of old farmland, and the pitcher's mound that Matty built in the backyard must have sat under a chicken coop back then. Matty inhaled some dust and got infected. The bad news is that Matty doesn't have enough marrow left for a transplant, even with treatment for the infection.
Foreman inserts a new IV into Matty and then makes a bold move. He can access marrow from Matty's hip bone. Doctors don't do that normally because it's painful and dangerous to access. He can't sedate Matty due to the infection and the boy will only have a little marrow left after this. Yet Foreman proceeds anyway. He straps Matty to the gurney and plunges a long needle into his hip. The boy shrieks in pain and begs him to stop. Foreman presses on.
His risk proves to be a success. Nick gets his transplant. The parents are mad, but the end result quells that anger.
House has a conversation with Foreman to see how he's handling all of this drama. Foreman is angst-ridden that he could listen to Matty screaming in pain and never question whether he was doing the right thing. He hates the idea that, in order to be like House as a doctor, he needs to be like him as a person. Foreman gives House his two weeks notice that he is quitting.