At Princeton General Hospital, Amber lies in the ICU hooked up to a ventilator, heart and respiratory monitors, multiple IVs, bags and drains. House and Wilson are there when her heart starts to race. The attending doctor notes that it only started in the last hour. House thinks that it is a delayed reaction to the trauma of the bus crash where she lost both kidneys and ripped up her femoral artery. He suggests bringing her back to Princeton Plainsboro by ambulance. Wilson pretends to be her husband and gives his approval.
Inside the ambulance, House starts to go through all possible symptom causes but Wilson is too consumed with grief to focus. Wilson asks why she was on the bus with him, but House doesn't know. Amber's heart flatlines. Wilson watches in fear as House prepares to shock her heart. Wilson proposes lowering her body temperature in order to keep her alive.
At Princeton Plainsboro, Chase works to connect Amber to the heart/lung bypass machine. The team gathers in the observation room while Wilson stands off alone, staring down at Amber. House thinks that the trauma must have stimulated a pre-existing heart condition. Kutner suggests ischemia -- an abnormality in one of her coronary arteries. He asks whether House could remember the symptom that he witnessed on the bus. House tells Foreman to run an angiogram and he has the rest search Amber's home for whatever would make her heart race. After the others leave, Taub questions what House was doing with Amber that night. Were they having an affair or doing drugs? House cannot remember, so Taub runs a tox screen just in case.
At Amber and Wilson's apartment, Kutner goes through her laptop and finds a video file of the couple in an amorous moment. He quickly shuts it off. Thirteen notes that treating a friend is clouding their judgment and their process.
House writes possible illnesses on the white board -- tachycardia, toxins, HHI and cardio angiography pending. He then writes the word DRUGS as well. House starts dreaming that Amber is in his office. She intimates that they had been meeting in secret and she pours him a glass of sherry. She slowly approaches House's chair and straddles his lap. Amber asks him if he feels "electricity." Suddenly, House jerks awake, alone in his office.
House is convinced he can unlock his memory with electricity by applying electrical impulses directly to the hypothalamus to evoke detailed memories. Cuddy and Wilson are reluctant. House's pager goes off. There is a jump on the EEG readout. House and Wilson enter to find the team waiting. The tests proved negative but Kutner shows them a bottle of vitamins that is really filled with prescription diet pills containing SSRI's and amphetamines. House wants to run a manual test to see if the valves of Amber's heart calcified by opening her up. House chastises Thirteen's lack of participation.
Chase preps Amber for open heart surgery with Taub and Kutner. When he goes to put drops in Amber's eyes, Chase finds that they are jaundiced. Her liver is failing.
The team assembles with Wilson. Thirteen says that Hepatic and heart failure could be caused by anti-trypsinase deficiency. Taub thinks Nocardia fits. Wilson wants to cool her body down further. House recounts his dream and asks if Amber drinks sherry. Kutner tells them that there is a bar called Sharrie's near the bus route. House has a flashback to "Sharrie's Bar." House orders that they fill her lungs with cold slurry to make her insides freeze. The team consider whether it is proper to have Wilson involved in the case and whether House's judgment is clouded as well.
House goes to Sharrie's Bar with Wilson. The bartender tosses House his keys and tells them he remembers House with a "girlfriend." House flashes back to being with Amber at the bar. The bartender remembers that Amber had sneezed. House says sneezing could be a symptom of an infection.
Kutner and Thirteen are removing Amber from the respirator and preparing to fill her lungs with super-cooled fluid. House finds Taub and Foreman looking at a video microscope. He guesses that the liver biopsy showed infiltrates and minor inflammation. It is Hepatitis B.
House has another dream where he walks in to Amber's room. Amber tells him that Hepatitis B is wrong. She shows him her back where there is a small, red rash. House wakes up and goes to the room where Taub and Foreman are with Amber. They gently flip Amber over onto her side to reveal the rash. The team urgently examines it. Taub thinks it looks like an influenza rash. Kutner says Dermatomyositis. House asks Thirteen to test the rash. Taub picks up a needle off a nearby tray. Thirteen then walks out. Taub carefully sticks the needle into the rash to see if pus comes out. He pulls back on the plunger and clear fluid oozes out. This means it is vesicular.
Foreman diagnoses Rocky Mountain Spotted Fever, which is treatable with doxycycline. House, Wilson and Foreman disagree on the course of treatment. Wilson says not to start her heart until they are a hundred percent certain of what she is suffering from. Foreman is furious and tells House that Wilson is wrong. They cannot allow emotions to dictate their treatment.
House comes to the women's bathroom where Thirteen is hiding in a stall. He asks why she is making mistakes. Is it because a young doctor like herself is dying? While Thirteen knows she might have Huntington's Disease, she won't get tested. House orders her to get back in that room or pack up her stuff.
Wilson sits vigil at Amber's bedside. Thirteen goes to the lab and draws her own blood for the test. Foreman goes to Cuddy to make her aware that House might kill the patient. Wilson argues with Foreman and Cuddy over treatment. The disease has moved to her brain. Thirteen, Kutner and Taub then put icepacks on Amber's body to cool her.
House and Wilson clash over treating Amber for anti-inflammatory or for infection. Wilson asks House to do deep brain stimulation to remember more. House wonders if Wilson wants him to risk his life in order to save Amber's. Wilson nods.
House's head is bolted into a stereotactic frame. Wilson assists as Chase carefully inserts the electrode into the hole above House's ear. House is transported in his mind back to Sharrie's Bar. The bartender takes a very drunk House's car keys. Wilson is there in surgical scrubs, but House realizes he had phoned Wilson that night. However, Wilson was on call at the hospital so he got Amber instead. House told her to have Wilson pick him up from the bar. Amber went to the bar and agreed to have one drink with House. She sneezed. House was so drunk that he left without his cane or paying the bill.
On the bus, Amber handed House his cane. She sneezed and said she was coming down with the flu. House remembers that Amber reached into her purse for pills and swallowed them down. Wilson is standing at the back of the bus. House says she has amantadine poisoning. The crash destroyed her kidneys and her body can't filter the drugs. Wilson is hopeful but House knows that dialysis doesn't clear amantadine out of the blood. There is nothing they can do. Wilson is stunned. In his memory, House sees the approaching garbage truck's headlights racing towards the bus. House starts to seize.
House lies in a coma, hooked up to several monitors. He has suffered a complex partial seizure, affecting most of his temporal lobe. The violent shaking widened his skull fracture, causing a brain bleed. "We won't know if there's any cognitive impairment until he's out of the coma," Foreman tells the team.
Meanwhile, Chase and a surgical team try to shock Amber's heart but they fail. Wilson is watching, trying to control his emotions. Cuddy enters Wilson's office and comforts him. She convinces Wilson to have Amber weaned off the anesthetics so that he can say goodbye to her when she wakes.
Chase dials down the anesthesia and leaves Wilson alone with Amber. Her eyes slowly flutter open. Wilson lies in the bed with his arm around her. Entwined, the two of them wait for the end. She says that it is time and he turns the bypass machine off. Amber dies.
House is still comatose, imagining he is on the bus with Amber. He thinks he should die instead. He is afraid that Wilson will hate him. Amber tells House to get off the bus. He steps off into the darkness, leaving Amber alone. House opens his eyes in the hospital room. Cuddy is there.
Thirteen gets the lab results confirming that she is positive for Huntington's. Taub returns home to his wife. Kutner watches television. Cameron and Chase join Foreman at a bar. Wilson, still stunned, stops at House's room. Their eyes meet but they say nothing.
Wilson enters his empty apartment. He lies on the bed and finds a note from Amber. She was telling him that she had gone to pick up House.