Teenage Dan shows up at his girlfriend Melinda's house. Melinda's mother Barbara makes Dan scrub up before being allowed in her daughter's bedroom. Melinda, who just received a transplant, complains to him about her crazy mother not letting her out of the house anymore. Dan and Melinda kiss, but hives breakout on her skin. Melinda begins to gasp for air and she swells up. Barbara quickly injects her with a shot of epinephrine for allergy attacks. She then accuses Dan of doing something wrong.
At their apartment, Wilson tells House that Cuddy called about a girl in anaphylactic shock. House would rather talk about their new living arrangement, but Wilson piques his interest. Although the girl is immuno-compromised, the attack happened while she was in a clean room.
The team is confused by Melinda's case. A person who received a transplant six months ago shouldn't need a clean room. The team settles on one of three lies. Either the boyfriend brought something in and is lying about it or the girl snuck out and is lying about it. The room might also not be hypoallergenic and the parents are lying about it. House orders a recheck of all parties and the room.
Foreman quizzes the family on their recent history. He doesn't see any reason for Melinda to stay home. Barbara pulls Foreman into the hall and explains that allergic reactions have almost killed Melinda four times already. Once it caused her to lose control while driving, which is what lead to the heart transplant. Barbara feels she's not protective enough.
Cameron and Chase examine Melinda's bedroom. One window isn't rigged to the home alarm system, and a nearby tree provides easy access. Was Dan doing some nocturnal climbing? At the hospital, Dan admits to Chase and Cameron that he snuck in Friday night and they had unplanned, unprotected sex. The doctors ask him for a semen sample so they can check Melinda for a semen allergy.
The test proves that she isn't allergic. Cameron assumes that Dan took every precaution before their encounter, but House wants facts. He pulls Dan out of Melinda's room and interrogates him on whether he has been taking antibiotics or penicillin. Dan admits that a friend's dad had some leftover penicillin, so Dan took it to prevent exposing Melinda to anything. He had no idea that she could have been allergic to penicillin or that he could have spread it to her through his sperm.
Cameron and Chase break the news to Barbara that Melinda is being released. Yet they don't tell her the specifics of this latest attack. Suddenly, Melinda begins gasping for breath and she vomits. Cameron realizes that this isn't an allergic attack. It is Melinda's heart.
The team reconvenes, now looking at congestive heart failure and anaphylactic shock which are two puzzle pieces from two different puzzles. Cameron suggests that the first episode wasn't anaphylaxsis but cyclosporine toxicity. House seems skeptical, and Foreman wonders what if it actually is two separate, totally unrelated incidents. House can't see how the two would be tied together, but Foreman presses to only look for a heart failure cause.
Foreman and Cameron perform a CT scan, but find no sign of coronary disease. Then they run blood work to rule out infections and a biopsy to rule out rejections. Melinda begins to worry that she's going to lose this heart. She knows the transplant only gives her five to ten more years, and she begs Foreman to convince her mother to allow her to enjoy the time she has left.
While at the apartment, House asks Wilson if he can think of anything that would tie together anaphylaxsis and heart failure. He questions if it is even possible for anaphylaxsis to not be anaphylaxsis, even if it responds to epinephrine. Wilson is too aggravated by House as a roommate to think of an answer.
The blood work and biopsy both come back negative. Foreman and the parents head back to Melinda's room but it is empty. Cuddy calls in a security alert. Noticing that Melinda left her clothes behind, they figure she must still be in the building. Foreman thinks she wants to be outside, and he races for the roof. He finds Melinda on the top stair. She complains that her mother is completely overbearing. Foreman patiently explains that she just had heart failure. Melinda cries that this all means that her mother was right all along. As they begin to walk back downstairs, Foreman notices that the girl has an odd gait.
Foreman examines Melinda in front of her parents. The steppage gait is a sign of extreme weakness or partial paralysis. Foreman then sees twitching above Melinda's knee and informs the family that it's fasciculation, which means that the paralysis is ascending.
With the paralysis ascending at this rate, the team knows it will Melinda's lungs in a few days. House wants to tie together the heart, anaphylaxsis and paralysis, but Foreman wants to focus on the paralysis first, since that's what will kill Melinda in the short run. He suggests Guillain-Barre based on the speed of advancement. House agrees with Foreman's line of thinking and orders an LP and an EMG.
The tests, which ruled out polio and West Nile virus, seem to point to Guillain-Barre, a disease in which the immune response goes haywire and begins attacking the peripheral nerves. Fortunately, it usually responds well to plasmapheresis. They begin the treatment.
The first treatment is ineffective. Melinda begins to sink into depression. Foreman explains to Barbara that mood swings are common with the medications, but Barbara believes that her daughter has finally given up. Melinda again begins gasping for breath. Chase quickly determines that it is not an allergy attack. Foreman, realizing the paralysis has reached Melinda's lungs, intubates.
Chase and Foreman call House. The paralysis is moving too fast to be Guillain-Barre. Cuddy wants an MRI to rule out a spinal lesion. The team reconvenes, searching for a new explanation. What if the boyfriend snuck in some food during the tryst and she developed botulism? House asks the team to inject a rat with Melinda's blood. If it develops botulism, their theory will be confirmed. Meanwhile, House is heading downstairs to browbeat Melinda into admitting whatever she's been hiding.
As Cuddy slides Melinda into a CT scan, House and Foreman interrupt. House accosts Melinda about the night Dan snuck in. He explains that Dan's penicillin caused her anaphylactic shock. Yet Melinda tells House that Dan actually took clindamycin, the same medicine that she uses. She saw the bottle. House and Foreman immediately realize this means the anaphylaxsis is still unexplained. Everything is connected.
When Melinda says that Dan hopped the fence before climbing, House says Dan must've dragged a tick in with him. House combs Melinda's body to look for it. Foreman reminds him that they checked for insect bites earlier and Cuddy scoffs at House's line of thinking. Melinda drops into heart failure. Foreman administers atropine. Cuddy calls for a bag of dopamine, then orders House and his tick search out of the room. Wilson says they have to get Melinda up to the ICU.
Wilson and Foreman wheel Melinda into an elevator. House blocks Cuddy from entering, then stops to elevator to continue his tick mission. Foreman hooks up one more bag of atropine, which buys House three more minutes. Melinda's heart rate drops to 56.
Cuddy and Melinda's parents race upstairs, only to find out that the elevator has been stopped. Cuddy angrily tries to cover. Inside the elevator, House is still adamant about the tick as Melinda's heart rate drops to 45. Foreman restarts the elevator. House thinks of one last place to check, and finds the tick in her vagina. The elevator doors open, and House holds the tick as Melinda stabilizes.