In the past, a doctor reassures two parents, Melanie and Ben, that their child has male and female DNA, genetic mosiacism. However, their baby can have a normal life once they perform surgery, but they'll have to choose.
Now, the parents encourage their son Jackson as he plays basketball. He passes rather than makes one shot. With seconds left in the game, Jackson gets the ball again and makes the shot, winning the game. He then collapses to the gym floor, suffering from pelvic pain.
Thirteen and Foreman are dressing for work in the morning and Thirteen tries to second guess House so that he won't guess they faked their breakup.
At the hospital cafeteria, House actually asks permission from Wilson to take his food. Cuddy arrives and gives him the case, and asks that he not tell Jackson that he could have been a girl. House readily agrees, surprising Cuddy. The team goes over the case and observes that the parents want everyone to make sure they don't say anything to Jackson about his testosterone treatments and claim they're vitamins. Foreman fakes an argument with Thirteen when she suggests a MRI to check for a blind uterus. House has them run a camera up Jackson's urethra. However, the parents arrive and confront House directly, and suggest he perform a MRI based on the research they've done. House gives in, much to everyone's surprise.
Taub and Thirteen run the MRI and Taub asks about Thirteen's relationship. He suggests they're both better off separated and that Foreman is like a robot. The test shows no indication of a blind uterus. Meanwhile, Kutner goes to see Wilson and describe what happened. Wilson suggests he simply enjoy it, but begins to have doubts himself.
Taub and Thirteen run a camera up Jackson's urethra and the boy's parents come in to encourage him. Jackson starts to have trouble breathing due to pericardial infusion and they're forced to drain the fluid. Back in differential, the team suggests theories unrelated to the boy's mosiacism and House has nothing to add. Thirteen suggests that testosterone use might have caused autoimmune disease, explaining the symptoms. House orders steroid treatments to block the testosterone.
Wilson goes to see Cuddy and accuses her of sleeping with House, explaining the good mood. Cuddy denies it and figures it's not a crisis. Meanwhile, Thirteen tells the parents to stop the testosterone treatment but they worry if they do that Jackson will revert. They ask Thirteen to tell Jackson that the testosterone blocker is something else. She suggests they tell Jackson the truth but Melanie and Ben don't believe it.
House meets with a clinic patient, Ian, who complains of pain in his limbs and demonstrates by poking them with a finger. House figures out that Ian has a broken finger. Cuddy wonders why Ian hasn't screamed for another doctor, only to see him emerge grateful for House's kind and courteous treatment.
As Thirteen gives Jackson the testosterone blocker, she discusses basketball and he admits that Melanie forced him to join the team. Jackson notes that he wanted to take dance but Melanie forced him to choose sports and his father gave in to her. Thirteen notices that Jackson's palms are red and they still don't know what's wrong with him.
Cuddy goes to see Wilson and informs him that his worse fears are correct: House is in a good mood.
Kutner talks with Foreman and offers his condolence on his breakup with Thirteen. Kutner figures it's for the best since Thirteen slept with women and Foreman won't have to lose her to another woman down the road. Wilson and Cuddy go into House's office and discover that he's unconscious and they can't wake him up. Kutner and Foreman notice and come in as Wilson realizes that House has stopped breathing. House suddenly revives, screaming, and Cuddy demands to know what is going on. Wilson figures that House knows what the matter is but he insists that he took too many Vicodin pills and asks about Jackson. The team realizes that House hasn't been taking Vicodin. House is more interested in discovering if Jackson is taking drugs and orders them to check the home. After House leaves, Wilson concludes that House is taking something stronger than Vicodin, possibly heroin.
Thirteen and Foreman check Jackson's room and Foreman asks if she misses sleeping with women. She tells him yes and then says she misses sleeping with other men, and figures he misses sleeping with other women. She wonders why he's bringing it up and they wonder if Kutner and Taub are jerking them around because they know. That means House knows, but Foreman thinks it's good since House either has to jerk them around or fire them, and he's not firing them. Thirteen finds a journal page detailing possibly suicidal thoughts and reads it to House. He is dozing but wakes up long enough to say he's unconcerned. Taub reports that he's discovered toxoplasmosis indicating an infection.
As they give Jackson antibiotics, Thirteen shows Ben and Melanie the notes, but Melanie refuses to discuss the truth with Jackson. Ben isn't so sure but Melanie insists that they could make things worse. Ben gives in and Melanie tells Thirteen to renew the testosterone treatments.
Foreman confronts Kutner and Taub, and Taub admits that he figured it out. Foreman wonders why House didn't notice and calls Wilson. Wilson is having lunch with House and Foreman soon realizes that House is there. House wonders why Wilson is buying him a drink and figures Wilson thinks he's on heroin. If House is on heroin, he can't risk drinking the alcohol. Wilson wonders if it's true and House takes a drink and then leaves.
Thirteen gives Jackson a testosterone injection but then tells him they're not vitamins and tells him to ask his parents.
Wilson finds House throwing up in the alleyway, and House explains that he's on methadone. It has twice the risk of death but it's legal. If he mistimes the dose, he can die. However, House boasts that it eliminates his pain entirely and tosses away his cane, then casually walks away.
Ben and Melanie go to Cuddy to complain about Thirteen and demand that she be removed from the case. Cuddy refuses to take Thirteen off the case and Melanie continues to insist that Jackson isn't ready for the news. Ben feels otherwise and says they don't have a choice. After they leave, Cuddy tells Thirteen to stay with Jackson since she's the only one he'll trust.
Ben and Melanie try to explain to Jackson about his condition and he thinks he's a freak. They disagree but he wonders why they lied to him. He tells them to get out.
House is reading in the bathroom stall when Cuddy comes in to tell him she knows about the methadone. She warns him he could die but House doesn't think it's any of her business. Cuddy forbids him from using methadone and House tells her that he's quitting.
Thirteen tells Jackson that he'll have to talk to his parents at some point but he refuses to hear about it. He talks about his friend Will and wonders if he really likes him, and if he's supposed to. Jackson points out he likes dancing more than basketball, and Thirteen tells him that he doesn't have to hide anymore. She shows him his poem that she found but he explains that he wrote it for an English assignment. Jackson starts to feel nauseous and then vomits blood. The hospital pages House, but he ignores the beeper and shaves off his stubble.
Foreman tells the team that Cuddy has put him in charge now that House is gone. Jackson now has necrotizing pancreatitis. Kutner wants to call House and Foreman informs him that he already tried and House isn't answering. Taub suggests scleroderma but Thirteen suggests Zollinger-Ellison and Foreman orders treatment. However, in private he points out that she favors that diagnosis because it isn't fatal, and she doesn't want to make the family feel worse.
Wilson goes to see House at his home and finds a woman leaving. House explains to Wilson that he hired a hooker to watch him breathe. Wilson is surprised to discover that House has shaved and is even wearing a tie for a job interview. Wilson has to admit that House appears fine.
Taub informs the parents that Jackson isn't responding to the Zollinger-Ellison treatment. Melanie confronts Thirteen and Cuddy intervenes. She tells Melanie and Ben to see Jackson regardless of his feelings, and then tells Thirteen she didn't do it for her. Cuddy returns to her office and Wilson admits that they may have made a mistake. Cuddy doesn't believe it and insists House doesn't "do" happy. Wilson thinks they should give House a chance not to be miserable.
Foreman and Thirteen are at home preparing to go to work the next day and Foreman tells her that Jackson's current treatment is slowing the progression of the disease slightly. Thirteen wonders her kidney function is improving, which would mean scleroderma isn't the cause.
House visits Cuddy to get a letter of recommendation. She says she's been busy and gives him the requirements for methadone treatment that he'll receive at the hospital. She offers him his job back and he agrees.
House returns to his office and Thirteen and Foreman inform the others that Jackson doesn't have scleroderma. House wonders when they came up with the idea and Thirteen lies. They go over the list of diseases they've ruled out and House wonders if Jackson drinks energy drinks. He goes to see the family and explains that Jackson initially had dehydration. The energy drinks strained his kidney and it took longer to rebound from the dehydration. The contrast material they injected for the MRI remained in his system and messed up his system. Jackson was fine when he arrived: it was the parents asking for a MRI that almost got him killed. Dialysis will clear out the contrast material and cure him.
Later, Thirteen talks to Jackson, who admits he's conflicted over choosing dance or basketball.
Cuddy comes to bring House his methadone. He admits that he screwed up by giving into the parents' request for the MRI even though he knew Jackson didn't need it. His good mood helped caused Jackson's problems. Cuddy points out he doesn't need pain to be a good doctor and House wonders why she wants him happy. She suggests that if he thinks his intellect his compromised, then he feels he has nothing. He throws the methadone in the garbage and limps out.