The episode begins in Boston's Hennington Mental Health Institute, where Joseph Slater, a patient, is muttering about "a girl in a red dress, with flowers in her hair." While he speaks, a man is performing brain surgery on him. He removes something from Slater's brain just as his look-out - the shape-shifter partner of The Agent Formerly Known as Charlie Francis - calls to say a guard is on his way to Slater's room. The man's partner steps out into the hall and shoots the guard and the two men flee, leaving Mr. Slater with his skull peeled back and his brain exposed.
Agent Olivia Dunham and Walter and Peter Bishop arrive at Hennington to look into the incident. A doctor tells them that Mr. Slater has been a patient for 14 years, suffering from acute paranoid schizophrenia. However, as of this morning, Slater is apparently sane. According to the doctor, Mr. Slater's brain is intact and he is in perfect health and is no longer insane. Seemingly, what the men did to Slater "cured" him of his insanity. Walter asks to see footage of Slater from when he was a patient. In the footage, Slater rants and raves about the girl in the red dress, who he believes lived next to her. The team reviews tapes of the break-in. Olivia recognizes the surgeon's face - it belongs to Thomas Jerome Newton, one of the frozen heads that was stolen from the cryogenics lab earlier. The same man that William Bell warned Dunham about.
Walter and Astrid discover that the doctor who sent Mr. Slater to Hennington, Dr. Simon Paris, also had two other patients. Dunham and Peter track one, a Mrs. Crampton, down to another mental health facility. She had suffered from a severe form of OCD - wherein she became fixated on the number 28 - for 14 years, just like Mr. Slater. And, just like Slater, she was recently "cured" of her OCD. Peter discovers a telltale scar on the back of her head - she had been operated on, too. Peter and Dunham look into Paris' third patient, also diagnosed with schizophrenia 14 years ago and also recently cured.
Walter realizes that all the patients were all given drugs for organ transplants, and surmises that Dr. Paris was using his patients' brains to serve as incubators for someone else's brain tissue. That explains the insanity, and also explains why these patients are now undergoing involuntary brain surgery: Newton is removing the brain tissue Paris had put in their heads. Astrid receives a disturbing call from Hennington: apparently, while Walter was a patient in his own hospital, Paris visited him six times. Peter checks his father's head and discovers the same scar that was on Crampton, albeit an older one. Walter is given an MRI, and Peter and Dunham learn that Walter did not have brain tissue implanted but removed. Peter compares the pieces that were taken from Walter against the pieces that were implanted in the Paris' patients and realizes they are a match. Peter theorizes that the pieces Paris stole from Newton must have contained Walter's memories on how he was able to reach William Bell's alternate universe. They realize Walter is in trouble, but it is too late: Newton has come for Walter.
Newton and the shape-shifters have Walter connected to the three jars holding the portions of his brain tissue. Newton shows Walter a series of pictures in an attempt to map his brain function by having him respond. Three of the pictures - those of a boy, a bowl of pudding and, chillingly, a coffin - remind him of Peter. However, the experiment isn't working. Newton decides that Walter needs to be in comfortable surroundings and takes him to his old house. The process works, and Newton interrogates a fully-functioning Walter. He demands that Walter tell him about "the door" that he built to the Other Side. Peter realizes that the rantings of the three Paris patients reveal that Walter is being held at his old home, but again is too late. He and Dunham storm the home to find Walter, but Newton and the shape-shifters have already escaped with the information they were looking for. As Peter tends to Walter, Dunham chases them down. She kills the two shape-shifters and detains Newton; however, he reveals that he has poisoned Walter and he will die unless Dunham lets him go. Dunham chooses to save Walter, cursing Newton as she rushes back to his side. Walter survives, and Peter subjects him to another MRI to make sure that he is okay. As the episode ends, Walter, encased in the MRI tube, flashes back to when Dr. Simon Paris visited him at St. Clare's. We see that Dr. Paris is actually William Bell, and he is removing the memories Walter has about creating the door to the Other Side. He says that what Walter has accomplished, the doorway, is just too dangerous, and vows to hide the information in a place only he can find.