|A woman is alone in her apartment, on the phone complaining about the lights that are flickering. As she hangs up, she notices some black goo on the coffee table. More of it drip from the ceiling and, as she looks around, more of it begins oozing out of the unwired electrical socket. She looks closer at the socket and sees an eye on the other side. She screams.
Sam and Dean arrive at the Roadhouse and walk in on Jo and Ellen in the middle of a screaming argument. Jo has a lead on a strange case in which several women have gone missing from the same apartment block over a number of years. She wants to investigate further, but Ellen will not allow it. Jo shows the paperwork to the boys, who are impressed with the level of detail she has come up with and take the case from her - to Jo's disgust and Ellen's relief.
They pick the lock to the apartment where the most recent woman vanished and take a look. There is some clear EMF which Sam picks up, and finds some of the residue from the electrical socket. They identify it as ectoplasm - a substance that is only created by a very bad-ass demon. They look around the apartment block further and suddenly find Jo, posing as an apartment hunter. She has lied to Ellen in order to chase up the case. Ellen phones Dean and asks if he's seen Jo, a question he lies about.
The three hunters collate what information they have on the building and any possible deaths. There is nothing obvious, so they decide to scan the whole building. Dean insists on keeping Jo by his side, and she reveals that her plan is to act as bait for the spirit. She yells at Dean that he is just being sexist when he makes a comment about her, but he tells her he has nothing against women - just amateurs. They can suddenly smell something unusual, and realise that whatever they are hunting is behind the vent in the hallway. Dean reaches in to pull something out he can see and ends up with a handful of long blond hair.
Meanwhile, another occupants of the apartment building is opening her mail when she too notices the black goo coming from the ceiling. The lights start flickering and cracks start appearing in the walls. She tries to get out of the apartment, but the door will not open. A hand appears in the vent, grabbing at her and pulling her into the wall.
Jo is still going through the notes she made, playing with her knife. Dean offers her a larger knife and picks up the one she was playing with. He looks at it and sees initials on it - WAH - William Anthony Harvelle. It belonged to her father. She asks Dean what his first memory was of John. He recalls being 6 or 7 and being taken shooting for the first time. Jo's strongest memory was seeing her Dad bursting through the door after a hunt like Steve McQueen. She explains to Dean that she wants to be a hunter in order to be close to her Dad. Sam bursts into the room, telling them that another girl has disappeared. They decide that the spirit is coming from the walls, but they still dont know who it is. Jo realises that the apartment building was built on a plot of land next to Moyamensing Prison - the place where H. H. Holmes, America's first serial killer, was executed. Sam recalls that Holmes created a "murder house", where he built fake walls and secret compartments so he could keep the bodies hidden.
They climb inside the walls to investigate further, but there isn't enough space for Dean, so Jo goes on alone. Suddenly, she sees the black goo coming through the walls. Dean, on his cellphone, hears her scream. By the time he gets to where she was, she is gone.
Ellen phones back and Dean reveals that Holmes has Jo. She heads out on the first flight. Sam identifies a possible location for a hidden area where Holmes is probably keeping the girls. Jo wakes up in a tiny space with barely enough room to move. She starts to cry and then composes herself, realising that she has to do something. She calls out and speaks to Theresa, the other woman who went missing. Both of them are trapped, but Jo assures her that they will be okay - her friends will find them. Holmes returns and reaches in, grabbing Jo and pulling out a chunk of her hair. Holmes speaks to Jo, who tells him angrily to go to Hell. He reaches back in and caresses her skin, but she uses her knife to stab at his hand, temporarily, at least, fending him off. He comes back, grabbing at her once more, but just in the nick of time, Dean and Sam arrive with the shotgun. They rescue Theresa, but Dean tells Jo that she is going to have to act as bait now.
She sits alone in the middle of the chamber, waiting. When Holmes turns up, she runs and the boys trap him by surrounding him with salt, trapping him in the chamber. They climb out and finish the job by pouring concrete down into the sewer, permanently sealing the spirit in.
They are in the car, sitting in silence. Ellen has finally caught up with them and they are headed back to the Roadhouse. Dean attempts to make conversation and turns on the stereo, but Ellen, in silence, switches it off. When they get back to the Roadhouse, Ellen asks for a moment alone with Jo. She reveals to Jo that she doesn't trust the boys any more than she trusted John Winchester. It seems that when Jo's dad died, there was another hunter there. John Winchester - he screwed up and got Bill killed. John never returned to the Roadhouse after that.