In Philadelphia, apartment resident Katie calls her landlord to demand that he check the faulty electrical wiring in her new apartment. As she hangs up, Katie notices a drop of a black tarry substance on the table. As she examines it, more of the substance drips down from the ceiling. It starts pouring out of an open electrical switch. As Katie looks at the open box, she sees a man peering at her from the other side and retreats, screaming.
At the roadhouse, Dean claims he's heading to L.A. to rescue Katie Holmes from an evil cult. They hear Jo and Ellen fighting inside and go back to investigate. Jo wants to go hunting, but Ellen insists she stay or go back to school. When the Winchesters come in, Jo wants to get their opinion, but Ellen tells them to stay out of it and then snaps at a family of Nebraska tourists who have wandered in. Before the argument can continue, the phone rings and Ellen takes the call. Meanwhile, Jo tells Sam and Dean about the disappearance of a Philadelphia girl three weeks ago. She notes that every decade or two, another blonde has disappeared from the same building, and that she did all of the investigating herself. Ellen gets off the phone and tells them to take the case, but she won't lose Jo.
The Winchesters drive to Philadelphia to check out the apartment. Dean admits that Jo put together a good file, but can't imagine her in the field hunting. They scan the apartment for EM activity and notice the open light switch box and a bit of the black goo,. which they identify as ectoplasm. Sam notes that it takes a powerful spirit to create that much ectoplasm. As they leave, they hear Jo talking to the superintendent, Ed. They ask why she's there and Jo claims that Dean is her boyfriend. Ed admits that his last tenant disappeared and stiffed him for the rent, and Jo pays him cash to take the apartment immediately. Once they're alone, Jo explains that she told her mother that she was going to Las Vegas, and put down a fake credit card trail to make it look convincing. Dean gets a call from Ellen, who asks if he's seen Jo. He lies and says he hasn't, and Ellen makes him promise to drag Jo back if she shows up.
The trio goes over the building plans, and Jo explains that the building was built in 1924, and converted from a warehouse a few months ago. Before that it was an empty field. They figured someone died violently in the building, but there's nothing in the history to indicate that. Dean questions her and Jo insists that she's covered everything, but he isn't convinced. They have to scan the building for EMF and Dean insists that Jo go with him. As they look around, he tells her that he's not going to let her out of his sight even though she wants to act as bait Jo figures he's a chauvinist, but Dean says the problem is that she's an amateur. He tells her that she has options, and a mother that worries about her.
As they scan the building, Dean and Jo become separated. Jo hears something at a grille and spins around, but there's nothing there. Dean comes back and smells something, but can't identity it. Jo scans the heating vent and picks up EMF, and Dean removes the grille. He reaches in and finds a hank of blonde hair attached to a piece of scalp.
Apartment resident Teresa Ellis comes home and checks her mail, and ectoplasm drips down from nowhere. The lights flicker and the ceiling begins to crack. The crack spreads as she watches, and Teresa tries to call out without success. She runs to the door but it refuses to unlock. The crack spreads down to the heating vent and blacked fingers reach through the grille and then through it, grabbing her leg.
Dean wakes up the next morning and Jo tells him that Sam went to get coffee. She admits that she spent the night going over the files. As she flips her knife around, Dean offers him his larger blade and she accepts it. As he examines it, he notices the initials WAH, and Jo explains that it belonged to her father, William Anthony Harvelle. Dean hands it back and apologizes, and Jo asks what the first thing he remembers about John is. He tells her about how John took him shooting for the first time, and gave him a smile of praise when Dean bullseyed every one. Jo tells him about her father sweeping her up in his arms when he'd return home from a hunt, and Ellen would start smiling again. She tells Dean that she wants to do the job as a way to be closer to her father, and Dean tells her there's nothing wrong with it. Sam returns and tells them that another girl disappeared
Dean confirms that Teresa disappeared around dawn and there's cracks and ectoplasm in her apartment. Jo finds a photo of the empty field where the building was built, and it shows a prison next door. They call Ash, who confirms that the other building was Moyamensing Prison, which was torn down in 1963. They executed prisoners by hanging them in the field where the apartment now stands. There are over a hundred names, but Sam notices one in particular, Herman Webster Mudgett. He realizes that it was the real name of serial killer H.H. Holmes. They confirm he was executed in 1896. Holmes was America's first serial killer, and used chloroform to knock out his victims, blonde women. Chloroform was what Dean smelled in the hallway the previous night. After he was killed, his body was buried in concrete to prevent mutilation. Holmes built an apartment building, the Murder Castle, which he used to capture and torment his victims in special hidden chambers, keeping them alive for days. Jo figures that Teresa could still be alive, and they prepare to smash the walls and find her.
Sam checks the first floor while Dean and Jo enter one of the passageways. It narrows so Dean can't pass through, but Jo insists on going ahead on her own. She finds an air duct and climbs down over Dean's objections. He takes another route around, and Jo drops to the next level. Ectoplasm starts to pour out of duct and she screams. Dean runs to investigate and smashes through the wall, but all he finds is her discarded cell phone.
Sam and Dean return to the apartment, and Ellen calls. She got Ash to talk and wants Jo on the line. Dean admits that her daughter has been captured, and promises to get her back. She tells them that she's taking the first flight out and hangs up. Sam notes that the Murder Castle had a basement, and there's an old sewer system below the apartment. Dean immediately heads out to check it out.
Jo wakes up in a narrow cell with a single slit in the door. The ceiling is covered with fingernail scratches and blood. Jo calls out and Teresa responds, and Teresa warns that Holmes is out there and is going to kill them. The ghost killer reaches through the slot and grabs a hank of Jo's hair as a souvenir..
Sam and Dean check the alley outside the building and use a metal detector to scan for the hatch covering the tunnel down. Once they get it open, Dean climbs down first.
Jo tries to kick the door open without success. Holmes whispers that she's so pretty, and Jo tells him to go to hell. He then reaches through the slot and caresses her until she stabs him with her knife. He retreats momentarily, but then returns, snatches the knife away, and covers her mouth with his hand. Sam and Dean arrive and open fire, driving him back. While Dean frees Jo, Sam assures Teresa that they'll get her out. However, once they free Jo, Dean tells her that they only plan they have is to use her as bait.
Jo waits for Holmes to return, and the ghost materializes behind her. Just as he's ready to grab her, Sam and Dean open fire, blasting open a bag of salt at the chamber's only entrance. As Jo ducks through the door, Holmes realizes that they've created a salt barrier around the entire room. Jo screams at him that there's no escape, and they seal the chamber for good.
Outside, Jo admits that she was scared, but she saved Teresa's life so it's worth it. She wonders what will happen if a storm washes away the salt. Dean arrives with a stolen cement truck and they fill in the chamber.
Later, Dean and Sam drive back in the Impala with Jo... and Ellen. She refuses to say anything and they proceed in silence. When they get back to the roadhouse, Dean apologizes for lying but says that Jo's father would be proud. Ellen tells them to go outside, and then says that Dean and Sam are just like their father. She hesitates and Jo demands the full story.
A few minutes later, Jo storms outside and tells Dean that she doesn't want to discuss it. When he persists, she tells him that her father had a partner on his last hunter: John Winchester. He screwed up and got Walter killed, and couldn't bear to come back and look Ellen in the eye. She tells Dean to go and then walks away.