In Chicago, Nancy Logan is walking home in the rain and steps over a discarded child's doll. She someone kneeling in a nearby alleyway and goes in to investigate. The figure stands up, turns toward the woman, and slashes her repeatedly with a scalpel. Once the woman is dead, the figure kneels down and starts cutting.
Sam and Dean drive into Chicago after Sam confirms that a serial killer is at large, having killed four people in the last six months. Each victim was a blonde-haired woman with blue eyes. An internal organ was removed from each body after the murder, and Sam figures that the organs were used for a Satanic ritual. He figures that it was one of the signs of demonic presence and wants to put an end to it so that no one else suffers like Mary and Jessica did. Dean agrees that it's worth investigating but tells Sam not to get too into it.
The brothers poses as Federal agents and meet with the Chicago detective heading the investigation. The detective admits that he has no leads and admits that the only fingerprints they found don't lead to any living person. The brothers go back to the car and Sam checks the Internet. He discovers that there was a similar spree of killings in Boston fifteen years ago. Similar kills stretch back, each in a different location every fifteen years since the 1960s. Each time, six women were killed, and Sam figures that the same person is responsible.
Police cars go by, their sirens on, and the brothers follow. Another woman is dead and when the Winchesters investigate the crime scene, they smell a familiar odor: formalin. Sam suggests that a reanimated body might be committing the murders, possibly a body possessed by a demon. He reminds Dean that the detective said that the fingerprints didn't lead to a living person. The brothers go back to talk to the detective, who tells them that the fingerprints belonged to Abigail Sullivan, who was killed in a car accident in San Francisco in 1962. Her body is buried in Santa Barbara, CA. Sam checks the computer records and discover that Abigail's husband Richard was in the car accident but survived. Richard was a medical researcher lauded for his innovative medical studies. Sullivan is living in Chicago and recently received a major medical award.
Sam and Dean go to see Richard, posing as magazine researchers doing an article on the loss of loved ones. Richard agrees to meet with them and talks about what happened at the time of his death. He tells them that they were driving home after their first anniversary celebration. When the accident occurred, Abigail was all but severed in two. She told Richard that she loved her before dying. Richard assures the brothers that he's over it and the Winchesters ask for a picture of Abigail. The doctor admits that he got rid of all of them in an attempt to move forward. A brunette woman comes in and Richard tells the woman, Michelle, that she should be in bed because she's ill. Michelle tries to gasp out a few words but Richard escorts her out. When Richard comes back, he explains that Michelle is his second wife.
Back at their motel, Sam points out that Richard and Michelle were both wearing cologne. Sam finds it suspicious because sick people don't like the smell of cologne, and suspects that Richard used the cologne to hide the smell of formalin. They call Bobby, who is near Santa Barbara, and ask him to check out Abigail's grave.
At Richard's house, Michelle is lying in bed, sweating and surrounded by children's dolls. Richard calls to ask if she's okay and Michelle gasps out that she's okay. She tells Richard to leave him alone.
Bobby finally calls the Winchesters back to tell them that Abigail's coffin is empty. There was a photo in the bottom and Bobby scans it and sends it to them. Abigail is in the photo and looks just like Michelle, right down to a conspicuous mole. According to the police reports, Abigail died of massive internal injuries so Sam figures that she needs the internal organs of women of a similar age to stay alive. She then approached Richard in her new identity to get close to her, and Sam figures that they have to stop her before Abigail claims her sixth and final victim.
The figure leaves Richard's house and goes out into the night. A blonde woman walks past and the figure goes after her. However, Sam turns, throwing off the blonde wig, and draws his gun. Dean arrives behind the figure and the brothers order their captive to drop the scalpel. However, the figure reveals that it's Richard, removing his wig. He tells them that Abigail wouldn't hurt anyone and that he killed the girls to keep her alive. Richard couldn't bear to live without her so he dug her up and used his talent to bring Abigail back. However, the organs he transplanted only last fifteen years so he has to seek out replacements.
Richard throws a scalpel into Sam's hand, disarming him, and then grabs his gun and takes him hostage. However, Abigail comes out and tells her husband that she doesn’t want any more innocents harmed for her sake. Richard realizes that she knows what he's been doing for her after sneaking out to follow him. Abigail hugs Richard and he assures her that it's not her fault. When he says that he can't live without her, Abigail promises her husband that she'll always love him... and then takes his gun and kills herself. Sobbing, Richard hugs his wife's corpse while the brothers look on.
Later, the police take Richard away and the detective in charge figures the brothers won't tell him because he's a local cop. Sam worries that he could go to the same dark place if he dwells on Jessica, but Dean tells him that Sam is nothing like Richard because he has someone to live for. The brothers leave, unaware that Meg Masters is watching them from the crowd.