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Sam receives an email from a friend in Stanford, Becky, whose brother Zach has been arrested for the murder of his girlfriend. Keen to help them out, Sam convinces Dean that they should travel to St. Louis. When they arrive, Becky explains that Zach came home to find his girlfriend Emily beaten to death. Becky claims that Zach was with her when Emily was killed, but that a security tape shows him arriving home around the time of her death.
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Claiming that Dean is a police detective, Sam gets Becky to take them to the scene of the crime. The only clues they find are that the house was robbed about a week before the murder, and that the dog next door has become vicious since the attack. Dean is still skeptical, but when he and Sam examine the security tape, which Becky has obtained from Zach’s lawyers. On the tape Zach’s eyes flare when he looks directly at the camera. Elsewhere in town, “Zach” watches a man leave his apartment and kiss his wife goodbye. His eyes glow silver. Later that night, someone who appears to be the same man, returns and tortures her.
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Early the next morning, Sam and Dean return to Zach’s house, as Sam points out that if the person they saw enter wasn't Zach, then he must have left by the back entrance to avoid being captured on the video camera. The blood smear in the alley behind the house supports this theory. They then see an ambulance pass, and follow it to discover that another murder has occurred, and in a striking similarity to Zach’s case, the man claimed to be driving home at the time his wife was killed.
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Dean and Sam find another bloody trail behind the apartment block, and follow it down a manhole to the sewer. On finding a pile of skin and blood they realize they are dealing with a shapeshifter. Suddenly the shapeshifter attacks them, and runs off. During their pursuit the boys are separated, and when they reunite at the car, having lost the creature, Sam suspects that Dean is actually the shapeshifter. As Sam confronts him the creature knocks him out and takes him prisoner. Dean's eyes glow silver.
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Sam regains consciousness in the sewer, bound to a beam. The shapeshifter has access to Dean’s memories, and claims that Dean is angry at Sam for having left him to go to college, and for having opportunities Dean never had. The creature finally leaves, telling Sam it has plans to attack Becky. At her house, Becky invites the shapeshifter, who she obviously thinks is Dean, in for a beer. They talk for a while, but eventually the creature attacks her. Suddenly a SWAT Unit arrives, and the shapeshifter flees, leaving Becky alive but bloodied.
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In the sewer, Sam struggles to get free, and suddenly hears Dean regain consciousness. Together they manage to escape, and as they walk the streets, see a police sketch of Dean on TV – he is now wanted in relation to Becky’s attack. They return to her house and Dean gets the Impala, while Sam distracts the police.
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Dean returns alone to the sewer to track the creature, and finds Becky there – the creature has assumed her identity now. Back at Becky’s house, the shapeshifter has tricked Sam, and is holding him captive. Sam tries to fight back, but gets overpowered.
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Dean arrives, finally shooting the creature who looks just like him. He snatches his amulet back from it. The police decide to release Zach, as they now suspect "Dean Winchester", who they found dead at Becky's house, was the culprit in Emily’s murder. As they leave town, Dean muses that he is missing his own funeral.