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Dean is furious at their situation, but Sam claims that they have no other choice. When Dean admits that he still does not trust his brother, Sam insists that he is still the same man, with the same memories. The pair arrive at a crime scene disguised as federal agents, finding the corpse of a dock worker with his heart removed. The next morning, Dean awakens to find that Sam has not slept, but has researched throughout the night and discovered a link between the two victims. They visit the house of Cal Garrigan, the brother of the dockworker, Ronald. Sam reveals to a hungover Cal that the first victim was his landlord, to whom Cal owed a large sum of rent. Cal admits that he got blind drunk and blacked out the night before, and the brothers suspect that he could be the werewolf.
Sam and Dean follow Cal as he embarks on another night of heavy drinking. However, he continues to drink with friends until dawn, without transforming. As the brothers leave, Cal drunkenly stumbles back to his truck, where he is confronted by the family dog, Lucky. The pet leaps at Cal and rips him apart, then transforms into a human male, covered in blood. The man returns to Cal's home, where he watches his victim's girlfriend, Mandy, sleep. The man returns to his dog-form and climbs up onto her bed. Mandy wakes up, annoyed by Cal's disappearance. Lucky follows her into the bathroom and watches as she takes a shower.

That night, Sam observes Mandy's bedroom and spots Lucky transform into a man. Exiting the house, the man makes contact with a shadowy figure and the two appear to argue. As the man returns to the house, his enhanced sense of smell detects the hiding Sam and he flees the scene. Sam chases after him, but discovers a pile of discarded clothes. Now in dog form, Lucky dashes across a busy road and is struck by a passing car. The guilt-ridden driver bundles the dog into the back of his vehicle and drives towards a vet, leaving Sam behind.
Back at the motel, Dean briefly considers calling Lisa, but tosses his phone away. Soon after, he receives a call from Sam, explaining that Lucky the family dog is a skin-walker. Sam reminds Dean that the creature is a cousin of the werewolf - they eat hearts and can infect you with a single bite, but can also be killed by silver. The brothers track Lucky to a dog pound and abduct the creature. In his human form, the skin-walker is tied to a chair in the brothers' motel room. Dean claims that he understand the walker's motivation to protect his family and demands that he reveal the identity of the man he met with. The walker reveals that his contact was another shape-shifter, explaining that a "sleeper cell" of 30 agents have been recruited to infiltrate families and lay low. When the time comes, the walkers are to infect the families, massively boosting their numbers in one night.

Inside the warehouse, the pack is angry with the skin-walker for committing murder without permission. They demand that he prove his loyalty by turning the captive Mandy and Aiden. Just in time, Sam enters and opens fire, while Dean also picks off the pack with his rifle. As the brothers continue to dispatch the pack, the skin-walker rescues Mandy and her son, securing them inside a locked room. One of the pack confronts the skin-walker and threatens to kill the humans. The walker transforms back into his dog-form, but his opponent is unwilling to participate in a "dog fight" and simply shoots Lucky. As the enemy walker moves forward to finish off his foe, Dean gets a clear shot and shoots him dead. However, when Sam arrives on the scene, he discovers only a pool of blood, and no sign of the wounded Lucky.
Sometime later, the skin-walker arrives at Mandy's home and apologises for endangering her and Aiden. However, she is unwilling to forgive and orders him to leave and never return. As Mandy watches from her window, the creature transforms back into Lucky the dog and walks away down the road. Meanwhile, Sam and Dean finally have a heart-to-heart. Sam admits that he does not care about Lisa and Ben, or even Dean himself. He confesses that he has done terrible things, including killing innocent people in the line of duty. Sam suggests that the lack of guilt makes him a better hunter, but also insists that he has fond memories of his old life and wants his soul to be restored. When he asks what they should do next, Dean replies, "We do what we gotta do, and we get my brother back".
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