Young wiseguy Joey Arnello eats in a hotel room. His brother and lawyer, Bill, is trying to talk him out of testifying. Joey stands up and, feeling dizzy, collapses. Bill tries to help him but the federal agents in the room think he's faking.
At the hospital, Vogler presses Cuddy for a budget on House's work. House comes in with a Federal Court Order issuing him to examine their witness. House wants out of it. Cuddy tells him to either see the patient or go to jail for contempt. After House leaves in a huff, Vogler tells Cuddy she needs to get rid of House or else give Vogler one good reason why they should keep him.
House examines the comatose Joey, who is non-responsive to bright lights and pain. He is nearly dead. Bill wants to know what's happening to his brother. House dismisses him, but Bill threatens House that Joey needs to stay in the hospital so that he can talk him out of testifying.
The MRI shows a subdural hematoma. House thinks those are pseudomembranes from an old injury, which wouldn't cause a coma. He asks about the liver, but Chase reports that the LFTs are only slightly elevated. Foreman wants to go into Joey's brain and evacuate the cavity, but Joey awakes and says that he doesn't want to be drilled. With Joey awake, House's team suggests releasing him. House overrules them, asking for hepatitis serologies and an auto-immune panel.
House learns that Vogler called admitting. They contacted the Justice Department, which came and checked out Joey. Cuddy tells Vogler that she can only control House. House demands to know who checked out Joey. Vogler says that he wanted to keep the government off the hospital's back.
However, Joey is rushed back into the hospital. After he's stabilized, the team begins examining his file again. Joey's liver is worse, but with completely different symptoms. Although tests for Hepatitis C came back positive, House doesn't think that explains the sudden onset.
House orders a biopsy, but Chase suggests starting Joey on Interferon to treat the Hep C first so that he will improve faster. House tells him to start the treatment but not to credit House for it. He also wants Chase to get a biopsy while he's at it.
House then holds Foreman back from the others and announces that he is pulling him off the case because somebody told Vogler that House lied to the transplant committee about House's last patient, Carly. House tells Foreman that he doesn't think he was the culprit, but he wants Vogler, Cuddy and everybody else to think that's what he believes.
Chase is in Joey's room explaining the Hepatitis C diagnosis, but Bill becomes angry. He slaps Chase with the warning not to mention that his brother has Hep C. He demands that Joey will not be treated for it. Meanwhile, Cuddy tries to save House from Vogler's axe. Although she hates House, she still wants to save his job. Vogler thinks that is proof that she does like him. This is bad for business.
Bill corners House about the disrespect shown to Joey over the Hep C diagnosis. House says that, between the jailhouse tattoos and blood tests, he's guessing that Joey was raped in prison. Bill admits that he heard rumors. Yet if this diagnosis gets out, Joey's reputation will be destroyed. House agrees to administer Interferon, but that he won't keep records on it.
Wilson lets House know that Cuddy has been locked up with Vogler for two days arguing about House's job. They notice a gleaming red '65 Corvette parked in House's spot. A note on the windshield indicates that it's a gift from the Arnellos.
Foreman rushes in with the news that Joey's blood pressure has dropped and he is bleeding into his liver. House gets the results of Joey's biopsy, which shows lymphocytic infiltrate and no bridging fibrosis. This means that Joey's condition is acute and not a result of Hep C. The other finding is that exposure to toxins has caused this liver failure. He was poisoned.
Joey's liver begins to shut down. Although they have to wait four hours until the next test results arrive, Joey's liver will only last two hours. House has an idea. A pig is brought into the hospital and placed next to Joey. An IV runs between an artery in Joey's leg and the pig's liver.
Cameron and Foreman continue the search for toxins. House notices from chest X-rays and white blood cell counts that Joey recently quit smoking. Outside of Joey's room, the two federal marshals in charge of guarding him argue. One of the marshals recently deposited $3,000 in his wife's checking account, and the other marshal questions whether it was a bribe. House interrupts them to announce that Joey took enough smoking cessation candy containing a Chinese herb to poison himself. He should be fine in a couple of hours.
That night, Wilson advises House to let Vogler tell the feds that Joey can be released since it is important to Vogler. This will also help House's cause. The next day, House dons a lab coat and enters Cuddy's office. He gives Vogler the news that Joey is free to go.
Cuddy examines the file and wonders how lozenges would cause such liver failure. House points out that it's a toxic match with Interferon. As Cuddy yells at House for altering Joey's medical file, House is paged. Joey has lapsed into another coma.
The team reconvenes to discuss causes. Chase again argues for Hep C, which they never really treated. House again notes that Joey's condition is acute and not chronic. Chase suggests an experimental treatment that's never been tried on humans using a non-nucleoside allosteric inhibitor to change the virus. Foreman phones a hospital in Philadelphia that's currently testing this treatment on dogs.
While seeing another patient, House has an epiphany. Sometimes the simplest answer is the right one. On the team's white board, House crosses out liver and estrogen. A discussion with Chase leads House to start thinking about what's causing the comas.
House approaches the federal marshal that made the recent deposit. Bill interrupts, saying they just gave the marshal some money to get Joey some decent food not on the hospital menu. House sees that Joey had a steak before each coma, and he mentions Ornithine Transcarbamylase Deficiency which is a genetic condition. If the condition is in the body and a patient eats a large amount of protein, the symptoms can come out. If House is wrong and they stop treatment, Joey will die.
House admits that he could be wrong because of Joey's increased estrogen level. But he has a theory. A product called Male Flame contains estrogen. It is marketed to gay men and sold on the same website that offered Joey's smoking cessation candy.
Bill adamantly declares that his brother isn't gay, but House thinks this is an overreaction. If he's so sure, they will continue Joey's treatment. Bill finally relents and Chase shuts off Joey's IV. Bill still can't believe that his brother might be gay. House points out that the only way a mob guy could come out of the closet is to change his name and move to another town. This is what happens after one testifies for the government.
After a few hours, Joey pulls out of his coma. He and Bill have a last conversation about the decision to run away. Bill calls the feds to announce that they are ready to make a deal. Even though they danced around the issue, Joey smiles at his brother's reluctant acceptance of his lifestyle.
Cuddy and House have another conversation. Cuddy says that Vogler threatened to fire her, but she told him that she was the only one who knows about the secret stuff that isn't in the books. So Vogler needs her. She wants changes. House has to do six more clinic hours a month and he must fire someone from his team. He has to choose between Chase, Cameron or Foreman.