After learning from a message from Gabriel that they need the rings of the Four Horsemen of the Apocalypse to seal Lucifer back in his Cage, Sam and Dean begin hunting Pestilence, following the trail of swine flu he leaves behind, but never arriving in time to catch him. They are left confused by the fact that Pestilence is using the swine flu rather than the Croatoan Virus. All that Bobby can tell is that Pestilence is still heading east which is of no help as the Winchesters are in West Nevada when talking to him. As they debate what to do, Crowley appears, telling them he has an idea. Enraged about his role in Ellen and Jo's deaths, Sam tries to kill him with the demon-killing knife, but Crowley just teleports out of the car when Sam tries and then gets their attention from outside, asking to talk. Sam accused Crowley of knowing the Colt wouldn't work and setting them up, but Crowley insists that he didn't know it would work. After dodging another attack from Sam, Crowley asks Dean to call Sam off because he can get them Pestilence. Crowley tells them that since he tried to help them kill Lucifer with the Colt, he has every demon in existence looking for him and he's taking a big chance trying to help them. He is able to convince Dean to give him a chance and they travel to an old cabin that's his safehouse. When asked how he found them since they have hex bags, Crowley explains that he had his valet hide a magic coin in their car when they last met and it allowed him to track them and hear what they discussed. Crowley explains that while he doesn't know where Pestilence is personally, he can get them the demon that does, the Horsemen's "stable boy." Crowley tells them that this demon knows where to find Pestilence and Crowley will be able to convince him to side with them since torturing him won't work. The Winchesters agree to go with Crowley to capture this demon. However, Crowley refuses to let Sam come along, claiming that its because Sam keeps trying to kill him. While reluctant, Dean agrees to go alone with Crowley as they need to find Pestilence.
At the same time, the demon, Brady, is working on getting Niveus Pharmaceuticals to distribute their swine flu vaccine fast as in reality, its a way for Pestilence to spread the Croatoan Virus, which is what's really in the vaccine. Brady reports back to Pestilence that their trials on the "vaccine" are coming along well and they will be ready for distribution soon.
Arriving at Niveus, Dean and Crowley spot a human security guard and rather than sneak in, Crowley slits his throat and lets Dean in. However, he refuses to go to the top floor where Brady is located and face the demons with him, telling Dean to tell Brady what Crowley told him to say and he'll be fine.
On the top floor, Dean kills at least one demon guard and meets with Brady who calmly offers Dean a seat and asks him what he wants. Dean tells Brady he heard that Brady was looking for War and Famine's rings since he and Sam took them from the two Horsemen and is willing to pay for them. Dean asks Brady to come with him to discuss the transaction, but Brady reveals to a shocked Dean that he really doesn't want the rings since War and Famine are now "withered husks" and giving them back the rings won't do any good. Instead, Brady wants revenge and he attacks Dean, sending him flying out into the hallway. Brady kicks him repeatedly, but Dean manages to get away and into the elevator without Brady being able to follow him. Upon exiting on the ground floor, Brady appears behind him and resumes his attack on Dean. Before he can hurt Dean too much, Crowley appears and drops a sack with a devil's trap on it over Brady's head and then bashes him in the head a few times with a crowbar, knocking him out. Dean is left annoyed that Crowley lied to him and nearly got him killed as Brady wanted him, not the rings, but Crowley is unrepentant.
Dean takes them back to the cabin with Crowley carving a binding link in Brady's chest to keep him from teleporting or smoking out. Crowley is reluctant to let Brady near Sam due to their past, but Dean decides to take him back anyway. As Dean ties Brady to a chair in the middle of a devil's trap, Crowley lets Sam know his displeasure. Sam is shocked to find out who Brady is as Brady had been his best friend at Stanford. The demon tells Sam he had possessed Brady during the middle of their sophomore year and Sam realizes that the demon had introduced him to Jess. Dean removes him from the room and insists that they need Brady to find Pestilence and get his ring. Eventually Sam goes to cool off, but Crowley is unable to convince Brady to turn so he decides to go after a nest of demons. After Crowley leaves, Sam traps Dean in the bathroom and confronts Brady. Brady tells Sam he possessed the real Brady during Thanksgiving of their sophomore year and used him to get close to Sam. When Sam was getting too normal, Azazel had him kill Jess to get Sam back into hunting. Brady taunts Sam, but Sam ultimately manages to keep himself from killing Brady and releases Dean.
After Dean is released, Crowley returns and reveals that he slaughtered a nest of demons, but left one alive and with the impression that Brady was working with him against Lucifer. Crowley tells Brady he will now be tortured forever unless Lucifer is defeated and demands Pestilence's location. However, at that moment, they hear a hellhound barking off in the distance and Crowley realizes that the demon at the nest slipped his own magic coin into Crowley's pocket to track him. Panicking, Brady promises to tell them whatever they want to know if they get him out. Realizing that they can't defeat the hellhound or escape, Crowley disappears. Dean attempts to hold off the hellhound with no success when Crowley returns with one of his own to battle the other hellhound. The group quickly flees the cabin as the hellhounds battle it out.
Moving to an alleyway, Brady gives the Winchesters the location of Pestilence and is pissed as he will now be tormented eternally. Crowley tells him its not going to last that long and leaves as Sam faces off with Brady, armed with the demon-killing knife. Brady taunts Sam, saying he hates demons because he's so like them, but Sam just says its an interesting theory and stabs Brady with the knife, killing him.