In Grants Pass, Oregon, roommates Ed Bright and Marshall Todd leave a bar and run into a woman in a white dress: Eve. She touches Ed’s face briefly and then goes past him into the bar. She locks the doors behind him and then walks in. A man asks if she’s okay and notices that she’s bleeding from her side. Eve says that she is and then steps forward and kisses him. She then walks through the bar, touching other people, while the first man goes berserk and attacks his friend. Everyone else that she touched goes berserk, attacking each other, while Eve watches in satisfaction.
Dean is busy making shotgun shells filled with the phoenix ash. When Sam and Bobby arrive, Dean notes that he spilled something on his arm and nothing happened. Sam suggests that it may only affect Eve, but Dean isn’t convinced. Bobby admits he hasn’t been able to find Eve, and suggests that Dean call Castiel. Castiel appears immediately and admits that Eve has cloaked herself against detection by angels. Sam suggests that they find a friendly angel to help them. A while later, he returns with Lenore, the vampire that helped them several years ago. She remembers them, and explains that Eve has been calling to her and the other vampires. The rest of her pacifist nest left and are hunting humans again, while she hid. Lenore warns them that Eve can see them through her, and she can’t help them. Sam insists that they can stop Eve and asks where she is, and Lenore tells them that they’re in Grants Pass, Oregon. However, she then asks them to kill her. Lenore says that she’s like the other vampires, and admits that she fed on a young girl and can’t stop. Before Sam can do anything, Castiel incinerates her with a touch and says that they’ve wasted enough time.
Castiel teleports Sam, Dean, and Bobby to Grants Pass and they see nothing unusual at first. They set up base at a diner and Bobby hacks the police database. There’s nothing unusual and Castiel offers to teleport through the town. However, he discovers that his powers have been blocked. Bobby goes Federal and finds a report by a local doctor, Silver, who called the CDC with an illness he couldn’t identify. The patient was Ed Bright. Dean and Castiel go to Silver’s office but his receptionist informs him that Silver is gone for the day. Dean tries to break into Silver’s office but spots blood leading to a shed. Inside is the corpse of Ed Bright, and Dean prepares to burn it.
Sam and Bobby check out Silver’s house. They discover he had a wife and two children, but they have all disappeared. The sheriff arrives and they claim to be FBI agents, and Bobby tells the sheriff to put out an APB. They then go to Ed’s house and meet Dean and Castiel. They see Ed Bright in the window and dean and Gam go in, loaded with silver ammo for shapeshifters. They find a half-dozen men in the house, all dead and all looking like Ed. One of them is alive, but says that he’s Marshall. As he dies, he tells them that he took Ed to the doctor, and they met Eve at the bar.
Outside, Bobby speculates that all of the roommates became shifters due to some kind of infection. They figure Eve is responsible and Castiel wonders why she would create an army of dying shifters. They go to the bar and find dozens of corpses. When they examine the bodies, they find that they all have vampire fangs but wraith wrist-spikes. The creatures appear to have died up from a high fever. The sheriff and his deputies arrive and arrest Sam, Bobby, and Castiel, but Dean hides before they can notice him.
At the station, Sam catches a glimpse of the deputies in the security monitor and realizes that they're shifters. They fight back, but the monsters overwhelm them until Dean arrives and decapitates one, and Castiel finishes off the other. They capture the sheriff and take him to the interrogation room, but it refuses to tell them anything about what's going on. They hear a noise outside and Sam and Dean go to investigate, and find two young boys, Joe and Ryan, locked in a cell. Sam recognizes them as Silver's boys from a family photograph, and they release them once they confirm that they're human. Joe, the older brother, explains that the sheriff and his men came for them. The Winchesters take them back to the interrogation room to feed them and question them, but they haven't heard anything about Eve. Joe says they have a brother in a town 15 miles away and Dean says they'll take them back. Castiel takes him to one side and insists that they have to focus on Eve, but Dean refuses and leaves with Sam to take the brothers to their uncle.
As Dean and Sam drive Joe and Ryan, Joe hugs his brother and Dean watches, smiling.
Bobby assures Castiel that they won't take long, but Castiel warns that it's a bad idea. However, Bobby says that nobody lets Sam and Dean do anything, and suggests they interrogate the prisoner again.
Sam and Dean reunite the brothers with their uncle.
The sheriff refuses to talk, and Castiel asks for five minutes alone with him. Bobby notes that he has no powers, but Castiel say she only needs five minutes. In less than five minutes, Bobby hears a single scream and Castiel comes out, wiping his hands. He has the address where Eve is holed up. The brothers return and find the sheriff's decapitated body. Dean distributes one shell to each team member and they head to the address. It's the diner that they were there earlier, and they wonder what game Eve is playing. Dean and Sam go in and tell Bobby and Castiel to come in shooting if they fail. Inside, Sam uses a video camera to confirm that everyone is a wraith. They start to leave, but Eve, dressed as a waiter, serves them two specials. When Dean suggests they go outside, the Starships draw the blinds, lock the doors, and take their weapons.
Eve is well aware that they have phoenix ash, and then says that she's not there to fight. She preferred the original arrangement, where they had an equilibrium of sort. But now her children are being tortured and she came to their defense. When Dean proves skeptical, she takes on the shape of their mother, Mary, to convince them. Angry, Dean tells her to kill them if she's going to, but Eve says that she wants Crowley. When the brothers point out that Crowley died months ago, Eve explains that he's still alive, and that Crowley wants the monsters' souls to achieve more power. To oppose him, she'll transform everyone on Earth into monsters. When Dean points out that it will take a while, Eve explains that she's building the perfect monster. The dead shifters are failed experiments, but now she has a replicating creature that can take over a town in a day. Finally, Eve says that they've had one with them: Ryan. She's satisfied that it can past a hunter's inspection.
The brothers' uncle comes to the living room and finds Joe, dead. He turns and confronts Ryan, whose mouth is covered in blood. Joe gets up behind him and the two monsters attack the man.
Eve says there's nothing they can do about it, and offers to let them live if they bring her Crowley. Dean immediately refuses and Eve warns him that he's out of options. Her monsters bring Castiel and Bobby in, and Eve explains that since she's older than Castiel, she can block his powers. She repeats her offer, but Dean insists that they aren't going to work demons or monsters. He dares her to turn them, and she bites him on the neck. After a second she falls back, gagging. Dean tells her that he drank the phoenix ash. Eve first reverts to her original form and then falls apart, dissolving from within. Once she's dead, Castiel's powers are restored and he kills all of the monsters. He then heals Dean, who says they need to find Joe and Ryan. Castiel complains that they don't have the time, but goes with them. They find the monsters dead on the cellar stairs, and sulphur traces meaning that demons killed them.
Dean and Sam figure that the demons killed Eve's monsters for a reason. Castiel asks for an explanation and is seemingly surprised to learn that Crowley is still alive. He says that he has to determine the truth and teleports away. Bobby has an idea and suggests that Crowley got away because Castiel meant to let him get away. Dean doesn't believe it, but Sam isn't so sure.
Castiel arrives at the diner and looks at Eve's corpse. Crowley tells him that he's tired of cleaning up his messes.