In St. Louis, James Frampton is playing off a prostitute in a dark alley. Once he leaves, the prostitute looks around nervously as she hears someone moving around. When she turns around, she finds James behind her. He flashes his badge and tells her that she's under arrested. Realizing that it's not her night, the prostitute turns around to be handcuffed... and James rips her throat out.
At home, James wakes up from his nightmare of murder. His dog leaps up on the bed with him and snuggles up, comforting him.
The next morning, James goes to the kitchen to make coffee. When he throws the filter in the garbage, he finds his shirt... covered in blood.
Sam and Dean arrive in St. Louis and decide to check into their motel and call James back in the morning. Dean isn't thrilled at helping James but Sam points out that he saved their lives a few years ago when they took on an alchemist. As Dean goes on a beer run, he asks Sam if he needs anything and hovers over him. Sam says that he's fine and Dean finally admits that he's not sure if Sam can take on the remaining two trials to seal the gates of Hell. Irritated, Sam tells him to stop worrying.
Once Sam is alone, he starts to work but hears something scratching at the door. He cautiously opens it and finds a dog outside the door. It runs past him and jumps on the bed, and Sam easily makes friends with it. When Dean pulls up outside, Sam goes out and claims that the dog came in on its own. Dean looks in and is surprised that there is an attractive woman in a black dress lying on the bed. She's wearing the same dog collar that the dog had and they figure that she's a shapeshifter. The woman speaks up and explains that she's a familiar, Portia, and she is bonded with James. Dean realizes that James is now a witch and Portia explains that after the alchemist case, James decided to learn witchcraft. He's used his magic to solve crimes and has been promoted to homicide detective. James has recently been suffering from headaches and nightmares, and she needs them to help. Dean points out that they don't trust witches but Portia insists that James has only used his abilities for good. Disgusted, she tells Dean to stop with the bigotry.
James goes to the local club where the city's witches meet. His friend, Spencer Wallis, comes in and talks to James. He admits that he's worried about James' condition and James tells him that he's been having nightmare. Neither one of them know anyone who could help James and Spencer points out that witches don't fit in anywhere. When Spencer asks about Portia, James admits that she has left him for the moment and worries that he's pushing her away.
At the motel, Portia explains that she's telepathically linked to James because of their witch/familiar relationship. She initially saw his thoughts when he thought he was killing people, but then he blocked her out of her mind. James finally blocked her out of her mind, but can't turn to the police or other witches because he doesn't trust them. Portia explains that she was the one who contacted them via text message and asks them to help.
A blind man is walking through the park and hears someone approach him. he calls out, asking who is there, and James dreams of himself ripping out the man's throat.
Sam and Dean visit James with Portia, and James angrily tells her that what's happening is none of her business. Once she leaves, James talks to the Winchesters despite the fact that Dean is clearly uncomfortable with the fact their friend is a witch. Sam focuses on the murders and James tells them that he's confirmed that the people he dreamed were dying actually died, in the way he saw them died. He shows them the bloody shirt and Dean wonders if another witch is controlling James into committing the murders. James has never heard of a mind control spell and the Winchesters agree to help. However, they insist on binding James with iron chains to negate his powers.
The brothers go back to the motel and Sam checks the crime reports. He confirms that each victim died the same way that James dreamed, and tells Dean that James was promoted to homicide detective practically overnight. Dean has collected the ingredients for a witch-killing spell that Bobby showed them, but worries that it might not work. Sam wonders if he's worried about the spell or about him, and is offended that Dean doesn't trust him. He figures that Dean's problem is that the only person he trusts is himself, but Dean focuses on the task at hand and warns that they'll only have one chance to cast the spell. When Dean points out that they may have to kill James, Sam reminds him that they've given other monsters in a past. However, Dean isn't buying it, noting that monsters like Benny and Kate didn't have a chance. He figures that James made his own decision to be a witch.
The brothers split up and Sam goes to the police station. He talks with the coroner, Josh, and the lead detective, Ed Stoltz. Sam shows him a piece of James' shirt with the blood and asks Josh to run a blood test on it. Ed tells Sam that they have a witness who has identified the killer as a man wearing a suit and a shirt that matches the one Sam brought in. However, Ed refuses to discuss the case any further with Sam.
Portia takes Dean to the witch's club so they can see if any of the locals know anything about mind control spells. As they go in, Portia tells Dean that she was the one who found James. However, she insists that she's no pet and that her soul and James' are bonded together. One customer, Philippe LeChat, calls Portia over and she introduces Dean as a Wiccan. As Dean starts sneezing, complaining that there must be a cat nearby, Portia asks Philippe where his master, Spencer, can be found. Philippe says that Spencer is around and asks Portia about James. She admits to Dean that most of the witch community thinks that he's making a mistake by working as a copy. Spencer comes in and Dean asks him if he know any spell that lets a witch control another witch. Spencer says that he doesn't think that it's possible and tells Philippe that it's time to go. Much to Dean's surprise, Philippe turns into a cat and leaves with Spencer.
Sam calls to tell Dean that Josh finished the blood work and confirmed that the blood on James' shirt came from the third victim. They figure that James is the killer and take him home. Portia chains James to the bed and he assures her that everything will be okay. They start to kiss and when they become intimate, Portia is able to read James' minds when he's off-guard. She sees flashes of all four murders and draws back in shock. When Sam and Dean come in, Portia tells them that James isn't a murderer. She did see the murders in his mind, but that was all she saw. There was no memory of him preparing for the murders or having a motive for the killings. The familiar figures that proves that someone planted the images in James' mind, and asks the Winchesters to pursue the investigation now that James is safely confined.
Sam goes back to the station and approaches Josh and Ed as they come out of room C-1110. As he approaches them, Sam notices that Josh is holding a folder with James' name on it. The two men hastily close the door and Josh walks away while Ed asks Sam why he's so interested in James' innocence. Sam says that they worked a case in the past, but Ed says that the police are handling the murders just fine. When Sam asks if James' quick promotion bothered anyone, Ed assures him that no one had a problem with it. He leaves and Sam checks the office door, confirming that it's locked.
Portia arranges a meeting between Dean and Drexyl, a local warlock who was James' snitch in the magic community. While they wait, Dean asks Portia which she considers herself, a dog or a woman. She figures that he's interested in her sexual relationship with James but refuses to discuss it. Drexyl arrives and tells them that he hasn't heard anything about a witch who could control other witches. The warlock does tell them that the magic community is up in arms over James' alleged killing and they figure that he'll have to either leave town or kill himself. Portia says that she won't let either one happen and Drexyl tells her that the other witches will kill James if he doesn't do it himself.
The brothers meet back at James' house and Dean checks Bobby's records and confirms that there is a spell that lets one witch plant false memories in another. Sam tells Dean what he saw and they figure that Ed and Josh are involved with the murders. After congratulating Dean on avoiding bestiality jokes, the brothers check on James. He tells them that he can astrally project his consciousness and check out the locked room. The brothers agree but only on the condition that James takes them with him.
James takes hold of the brothers' shoulders and casts the spell. He then enters the locked room and the three of them see all of the evidence that Ed and Josh have gathered against the killer... James. Among the papers is a witness statement from Philippe testifying that he saw James commit one of the murders. James breaks the spell and explains that Ed always wanted a big case to make his career. Further, Ed was the one who was demoted as lead detective on James' first case that he solved. Thanks to Philippe's statement, Ed has all of the proof he needs to put James away. Furious, James knocks the brothers out and tells Portia to leave before she gets dragged down with him.
At the bar, James bursts in and grabs Philippe, demanding answers. The familiar tells James that Spencer told him to lie, and then his neck suddenly snaps. James turns around and discovers that Spencer is there, casting the spell that killed Philippe. James figures that Ed is blackmailing Spencer into framing James, but Spencer smugly explains that he engineered the frame to make James appear to be a killer. He tells his supposed friend that he always wanted Portia as a familiar. Even when he lost her to James, he was willing to tolerate the situation. However, when Portia and James fell in love and made love, it was the last straw for him.
Sam and Dean arrive, ready to cast their spell, but Spencer knocks them back and then levitates James into the air, crushing his body. Dean tries to cast the spell but Spencer freezes the brothers in place by forcing them to relive their memories of the worst experiences in their lives. Portia transforms into her dog form and leaps at Spencer, disrupting his concentration and knocking him to the floor. He manages to knock her back but the Winchesters cast their spell, killing him.
Later, James and Portia prepare to leave town, realizing that the witch community won't tolerate their relationship and the police will arrest James for the murders. Portia admits that it's not the first time it happened to them and won't be the last. After the couple leaves St. Louis, Sam and Dean hit the road. Dean apologizes to Sam for failing to trust him, and explains that when he relived all the memories of the pain, he realized that he only survived them because Sam was there for him. He tells Sam that he trusts him and figures that if Sam says he's good then he's good. Sam says that he's good... but then makes sure Dean doesn't see that he's coughing up blood.