A young woman named Addie becomes dizzy in her karate class. She begins coughing up blood. Later, at the hospital, the team reviews the case. Cameron postulates drugs, toxins or infection. She figures that if Addie coughed up blood, then it came from the lungs. However, Addie has no fever or elevated white count, which rules out infection. A blood panel was negative for toxins and her bronchoscopy showed pristine lungs. Cameron then assumes it must have come from the girl's stomach, indicating an ulcer or GI bleed. Yet the ER also did an upper and lower GI. There's no occult blood in the stool, meaning no ulcer or GI blood. Basically, the blood didn't come from anywhere.
House enters asks the team if they've figured out yet that the blood came from nowhere. Cuddy pulls House and Foreman out into the hallway to inquire about Foreman's resignation. He's sure that he still wants to quit. Cuddy has him sign a form to make it official. House wonders why Cuddy isn't begging him to stay. She thinks it wouldn't make a difference. Back in the office, Foreman breaks the news to Chase and Cameron.
Resuming Addie's case, Chase mentions the possibility that a hyperdynamic heart could have forced too much blood into the lungs. It wouldn't leave a trace because the blood came from the veins. House orders Foreman to run an echo stress test on Addie. He sends Cameron to check out the girl's dorm before re-running the ER labs.
While performing the echo stress, Chase asks Foreman why he's leaving but Foreman doesn't give up anything. Chase wonders if that means Foreman is embarrassed about the reason. Addie's heart rate spikes to 170 and Chase can only see goose bumps on her arm. House still thinks it's an infection. He instructs Foreman to start treatment and get a lung biopsy. When Foreman leaves, Chase asks House why Foreman has resigned. House answers that Foreman has decided to raise llamas. Chase realizes that House is also ashamed of the real answer.
House tells Wilson that Foreman is leaving because he doesn't want to turn into another House. Wilson yawns, which House finds intriguing, and then suggests he try to bargain with Foreman. Maybe he can offer him a raise.
As the doctors discuss Addie's case, House asks them what pandiculation is symptomatic of. He is pretending this is in reference to Addie when really it's to learn about Wilson. House then makes a lame joke that Foreman chuckles at. Chase stops short, accusing Foreman of doubting his decision. He's never laughed at one of House's jokes before, but did now because he's nervous. House begins to realize that he was wrong about the infection. He tells the team to attend to Addie before she crashes. They rush in with the crash cart to find her gasping for air. The doctors slide a laryngoscope down her throat.
Chase later explains to the group that Addie couldn't breathe because she had a pleural effusion, which indicates either cirrhosis or heart failure. However, her heart is fine and the liver enzymes are normal. House keys in on the fact that there was blood in the pleural effusion. This confirms his supposition about infection, but Chase argues that it was only minute traces of blood in an otherwise clear liquid. House orders them to double the dosage of antibiotics and check the lungs with an arteriogram.
The arteriogram test comes back normal. House is still convinced it's an infection. The team is skeptical that Addie would keep fighting off an infection that returns, but House wonders if maybe she's missing a protein that cannot be tested. Picking up on his lead, Chase blurts out the disorder of complement factor H deficiency. That would mean Addie is as good as dead. Her body cannot fight off bacteria, and she will succumb to one infection after another until her body shuts down. Since there's no diagnostic test for complement factor H deficiency, House wants them to isolate the cells that are most attractive to that affliction. They need to stick a needle in her eye.
Despite the case, House is still subject to clinic duty. He treats a man named Steve who complains of floating stool. Accompanying Steve is his girlfriend, a free-spirited nutritionist named Honey. She is disappointed because Steve has been cheating on her by eating meat. House sees this as an opening to ask Honey out. She accepts.
House crushes up some amphetamine pills and secretly drops them into a cup of coffee for Wilson. Wilson is naturally suspicious of House being nice. So he grabs the cup that House isn't offering, but that is the one filled with the amphetamine.
Addie's macular biopsy comes back negative, proving that it is not complement factor H deficiency. House still thinks it's an infection. They take a brain MRI, and Addie cries out during the procedure that her head hurts. When the doctors pull her out from the machine, they are shocked to see that the top of Addie's head has somehow burst open, leaving blood and tissue oozing onto the table.
The doctors anesthetize Addie and begin debriding the tissue. Foreman notes massive tissue death and Cameron notes that it doesn't have any pus, which should rule out infection. House again refuses to back off his diagnosis. Chase thinks it's more likely to be autoimmune, which means they need to start steroid treatment immediately. House invites him to proceed as long as Cameron stands by with the crash cart. If Chase is wrong, Addie's heart will give up almost as soon as they start with the steroids.
House stands by in the hallway as Chase starts the steroid drip, eagerly anticipating the massive heart attack. Yet nothing happens. Cameron smiles and turns the crash cart off. House is somewhat annoyed.
Wilson calls Foreman to his office. Foreman immediately notices that Wilson is going a hundred miles an hour. Wilson blurts out that House wants Foreman to stay. Before he leaves, Foreman says that he knows House is a good doctor.
Wilson tracks down House at home and angrily accuses him of drugging the coffee. When Wilson yawns, House is positive that the yawning is a symptom of something else. He posits that Wilson is taking anti-depressants. House says he would be on them as well if he wasn't in denial about his depression.
That night, Cameron wakes House up because he wasn't answering the phone. She informs him that Chase was wrong. Addie's kidneys have shut down. House actually smiles at the news.
At the hospital, Cameron announces that hemolytic uremic syndrome is what caused Addie's kidneys to shut down. House remarks that this is usually caused by an infection or a protein deficiency. House gloats that he was able to diagnose an invisible disease based on coughed up blood. The team is more interested is what they're going to do next. If House is right, the steroid treatment means that Addie's next infection will be ferocious. So they decide to wait for a stroke or heart attack to confirm an infection.
Eventually, Addie suffers a heart attack. The doctors are barely able to save her. Foreman gives the news to House then asks if he even knows the patient's name. House doesn't, but he argues that this is not what is important to him or the family. House thinks Foreman doesn't want to quit. Foreman asks if that statement actually means House doesn't want him to quit. House scoffs that Foreman is under the impression he can make House a gentler person. Foreman cuts him off, charging that House is about to tell a young girl she's dying but all he can think about is himself. Foreman hopes to God he's not like House.
House walks into Addie's room, apologizes and then tells her she's dying. The infections will continue to get worse. She has two days or less to live. House attempts to explain the disease, but she doesn't want to hear it. House is amazed that Addie doesn't want to know what's killing her. She questions whether knowing will make her live longer. House wonders what life is without curiosity. As he talks about diagnosing problems, Addie notices that he is smiling. He catches a reflection of himself and she's right. House is actually smiling as he talks about this in front of a dying girl. He abruptly exits.
House barges into Wilson's office and blames him for dosing House with anti-depressants. Wilson smiles, unable to hide the truth. They've obviously worked. A miserable girl just noticed how happy he was. House counters that she wasn't miserable and has been in that same mood all along. House freezes with an epiphany.
House barges into Addie's room and orders her parents out. He sits down and tells Addie that depression manifests itself in many different ways. She tried to kill herself by downing kitchen cleanser. Since she is intelligent, she knew that it would sting her mouth and throat. So she must have wrapped the cleanser in a gel cap, which burned a hole in her intestine yet left no other trace behind. Scar tissue fixed the hole but also formed a bridge between a vein and an artery. Instead of her veins sending bacteria into her fecal matter where they should be eliminated, the bacteria was being sent back into her system. Yet does Addie want them to fix her? Surgery will only take two hours but the psychotherapy will take longer. Addie cries, confessing that she's never been happy. She begs House not to tell her parents because they will blame themselves.
As surgeons work on Addie, Cuddy tells Foreman that House isn't actually that bad. She questions whether he really is afraid of turning into House. Foreman says it's not worth it and leaves.
That night, House meets Honey at a bar. He orders the same peppermint tea that she's drinking. Honey is under the impression that House is interested in hiring her as a nutritionist for his team, but House has another, more personal, relationship in mind. He points out that he hates tea. Then he lists all of his many shortcomings. Honey is not put off by any of it.