Two college students are sparring at a dojo when the girl Addie becomes increasingly violent then collapses, spitting blood. The staff checks her out but they're more interested in the fact that Foreman has announced his resignation. House orders tests and while Chae tries to get an answer from Foreman on the reason for his resignation, Addie displays goosebumps. House suspects an infection in her lungs and orders a biopsy, then goes to see Wilson and notices he's yawning. Wilson simply claims he's tired and wonders if House doesn't believe Foreman is quitting.
Addie's tests prove negative but House wonders what might cause her to display the symptoms of an infection. Foreman laughs at one of House's jokes and Chase wonders why Foreman now finds his superior humorous. Addie goes into convulsions and they run a spinal tap. There are minute traces of blood in the sample and House believes this indicates an infection, and orders his staff to check the lungs. He then meets with a clinic patient and his girlfriend, a nutritionist named Honey, and the man complains about floating bowel movements, and he's a vegan. While he goes out to pick up some amphetamines, staff report that Addie's lungs are clear but House still believes there's an infection and they suspect her body is unable to fight infection and they should try to fight the continuing infections. House then returns to say that Honey's boyfriend is cheating on her… by eating meat.
Chase administers a macular test to Addie by checking her eyes, while House grinds up the amphetamines and puts them in a cup of coffee which he gives to a suspicious Wilson. He then talks about hiring Honey, then the staff report the test was negative but House believes he's still right about the infection. They go with a MRI and Foreman admits to Cameron that he's quitting because he doesn't want to be like House. Foreman admits he thinks Cameron is a jerk and he is becoming a jerk like House. Addie's head starts to hurt and she starts bleeding from the top of her skull.
House believes an infection is still responsible and Chase wants to give her steroids for auto-immune, but it will kill Addie if they're wrong. They prepare for a heart attack which will confirm House's diagnosis, while Cuddy confronts House and wants to know if he's talked to Foreman about his resignation. Cameron holds off on shocking Addie.
Foreman goes to see Wilson who is unwittingly on amphetamines. Wilson tells him that House wants him to stay, then goes off to see a patient and makes her nervous. Wilson figure out what's going on and confronts House, who cheerfully admits what he did and notes that Wilson is still yawning, which means he's taking anti-depressants and has to take Vicodin to calm down.
House goes to bed and wakes up to find Cameron over him. She tells him that Addie's kidneys have shut down and Chase was wrong. The new symptoms confirm an infection and the steroid treatment will make the next infection worst. House is happy that he diagnosed it early on but wants to wait until she has a stroke or heart attack to confirm.
Addie finally goes into v-fib and Foreman brings her back, then congratulates House. He notes that House doesn't know her name or her parents' name, but House isn't concerned. House figure Foreman doesn't want to quit when he notices Foreman is trying to get him to mellow a bit, and won't admit he wants Foreman to stay.
House goes to break the news to Addie and her parents and she doesn't to hear why she's dying. House prepares to leave then wonders why she's not interested and is smiling and happy. House finally realizes what he's been missing and goes to Wilson, who's recovering from amphetamine withdrawal. House realizes that Wilson has been slipping him anti-depressants in his coffee, making him "happy." House realizes he's been missing something else… and goes in to kick the parents out of Addie's room while telling them she'll leave. He realizes she's been suffering from depression and tried to killer herself by taking kitchen cleaner that she put in a slow-dissolving gel cap. Her body started to heal the damage but damaged the veins causing a "bridge" that let the bacteria into an artery and spread throughout her body. She admits she's never been happy and asks House not to tell her parents. He agrees in return for her promising she won't do it again and she does, but House is skeptical.
Surgery fixed Addie and House breaks the law and tells the parents what really happened, then suggests they might get her on meds. The parents want to call her if they have any questions, and House tells them no.
Cuddy meets with Foreman as they watch Addie's operation, and tells him there are worst things to turn into, but Foreman doesn't believe it. House meets with Honey at a bar and it turns out he wants to date her. He lays out all of his character flaws but she's impressed with his truthfulness and he has a cup of her tea… when he hates tea.