House is in the ER of Middletown General Hospital after crashing his motorcycle. The patient in the bed beside him is Lee, who sees his attending Dr. Kurtz engaged in conversation with another doctor about Lee being an organ donor and brain dead. Lee calls out to Kurtz, but the doctor doesn't respond. House looks at the EEG readout and points out to Kurtz that Lee still has minimal brain waves. Lee is not able to speak. House approaches Lee's face and asks him to blink, which he does, indicating locked-in syndrome. Dr. Kurtz examines Lee and tells him that he was in an accident. Lee remembers riding his bicycle on a rainy street when a door from a parked car swings open as he smashes into it. The traumatic injury has damaged Lee's brain but House theorizes that perhaps the brain damage actually caused the accident.
Lee's wife, Molly, visits him. He communicates by blinking his eyes. House tries to examine the patient's catscans but Dr. Kurtz catches him. Lee sees Foreman, Thirteen and Kutner enter to visit House. Foreman says that, next to trauma, the most likely causes of locked-in syndrome are basilar artery stroke and brain hemorrhage. Thirteen suggest that Lee has a brain tumor.
House manages to get Lee's paperwork and he orders an MRI. The MRI video goggles that cover Lee's eyes show a beautiful beach scene. Lee sees House on the beach with him and tells House that he was sent from God. Lee sees his children on the beach and runs to them. Suddenly, Lee is back in his patient room. House is there, and shows Lee that his MRI indicates cancer-causing paraneoplastic syndrome. Dr Kurtz thinks that it is Eastern Equine encephalitis. Lee looks up and sees the antivirals hanging from the IV above.
House has a one-way conversation with Lee, who starts seizing. As Molly grills Dr. Kurtz, House interjects that a seizure would happen if it was really cancer. Dr. Kurtz denies that it is. House rebuts that Lee has a small tumor in his brain stem and he needs plasmapheresis.
Lee is wheeled into Princeton Plainsboro. Cuddy tells House that the plasmapheresis is all set up as she touches his face. Lee notices their intimate interaction. When Taub approaches, House tells him that he has decided to accept his previous resignation. He gives Taub an ultimatum in order to keep his job -- he must save Lee.
House's cell phone rings and Wilson comes up to him. He asks why he went to Middletown and suggests that a nearby pain clinic was the real reason. Taub is setting up the plasmapheris when Kutner enters. House wants them to engage Lee to keep his mind working. They notice something wrong with the patient.
House enters Lee's room with the team and asks if he is a drinker. Thirteen brings up Macchiavi Bignami Disease and Kutner mentions Wernicke's. House wants to biopsy the brain stem. Thirteen tends to Lee because he has had blood in his urine, and she places a new catheter into his groin. Lee's family comes to visit.
Chase performs the biopsy on Lee, whose mind wanders back to the beach with House. After the surgery, Chase asks Lee questions but Lee can no longer blink in reply. House and Foreman explain to Lee why his eyes are not moving. The biopsy revealed severe damage to the myelin sheath. House wonders if he is already dead. Taub has an idea to connect Lee to a brain computer interface (BCI), which records brain waves and thoughts. Lee is unresponsive.
Wilson comes to see House in his office to find out about why he was out of town. House tells him that Foreman's brother is in the Downstate Correctional Facility in Fishkill. Meanwhile, Taub sits with Lee and pours his heart out about his own life. Suddenly, the BCI computer makes a sound. Lee communicates to his wife through the computer.
House and the team question Lee about his health. They ask if he traveled to St. Louis last week, which catches him in a lie to his wife. She and House assume this means he was cheating on her. House tries to learn where exactly Lee was. In Lee's head, he and House are transported to Middletown, where House asks him about his location. He narrows it down to a friend's house.
Taub and Kutner visit that home's basement, where they find Lee was looking for a job from there. Lee explains that he didn't want to worry his wife. Taub and Kutner find that Lee worked as a janitor at a battery factory. Inspecting the factory, they see metal filings on the floor which Lee had swept up. He must have heavy metal poisoning.
As Lee is treated on chelation, Taub is pleased that his idea was a success. Foreman treats Lee's eyes that need constant irrigation and talks to him about having bought Thirteen jewelry that he hasn't seen her wear. Yet Lee has seen it on her. Molly talks to Lee about him keeping their money troubles a secret.
Taub asks House about keeping his job. He wants to overcome his fear of working there so that he can feel useful. House is not satisfied with Taub's idea about the computer mind reading; he wants more from him. Thirteen and Foreman tend to Lee's eyes and find he has ulcerative keratitis, which means that metal poisoning is not the thing making him sick.
Cameron comes to House's office to dress his wound. He says that ulcerative lesions indicate a virus, so they are back to infection. It could be Varicella or an auto-immune disease like Behcets's. Cameron suggests that they can narrow it to Varicella if they can find polys, or else it is Behcet's if they see lymphs.
Wilson chats with House in the cafeteria. He knows that House did not see Foreman's brother in jail. He really was checking on a woman that he thinks Wilson is seeing, who is a caretaker of Wilson's brother.
Foreman administers a lumbar puncture to collect fluid from Lee's spine. Lee flatlines and his mind fades away to the beach, where House tells him that he is about to die. As the team tries to deal with this development, Lee has given up and wants to pass away. He indicates to them on the computer that his foot itches. House says this means liver failure. Thirteen suggests that a dying liver can lead to locked-in syndrome. Foreman adds that it is most likely Sclerosing Cholangitis.
As the team biopsy Lee, Kutner asks why Thirteen isn't wearing her new bracelet any longer. She says it is because Lee urinated on it. Kutner points out that she has a rash where it was on her skin, and perhaps it is an infection. Kutner theorizes that Lee could have picked up something if there was a rat in the basement where he camped out. They find a small paper cut on his finger that could have been the entry point for an infection that went to his brain and destroyed his liver. They will treat him with Penicillin. Kutner tells Lee that they found rats in the basement that tested positive for Leptospirosis. Lee is able to move his finger. He is "un-locked."
House enters the locker room to find Taub and Kutner getting ready to leave. Taub takes credit for the rat theory. After he exits, House asks Kutner if he is fine with Taub stealing credit. He says that he is. House is pleased because the fact that Taub did it shows that he cares. He is also pleased with Kutner coming up with the rat infection.
Wilson catches up to House in the hallway and gives back the cell phone that he swiped from him. Wilson checked his call log and found that House is actually seeing a psychiatrist in Middletown. They enter Lee's room and House pulls out a digital micro-cassette recorder from under Lee's pillow. Lee grabs his hand and tells him he was sent from God. Wilson chastises House for spying on his team. Wilson wants to know why he decided to seek help, but House says that he is not going back to therapy. House enters the elevator and Wilson tells him that he is going to end up alone. The doors close.