After a group of young girls go missing Sam and Dean realize that a group of vampires have taken up residence in the small town. After a fight with two of the blood-suckers, Dean is bitten and turns into a vampire. Samuel tells Dean he can change him back but he’d have to get the blood of the vampire who turned him. Dean infiltrates the nest and runs into the Alpha...

Meg kidnaps Sam and Dean and tries to force them to tell her where Crowley is hiding. Sam makes her a deal - they will help her find Crowley if she promises to torture him for information about how to get Sam's soul back. Castiel joins the fight but finds it difficult to work with Meg.

Eve, the Mother of All, unleashes a new monster upon the world: a black worm-slug that can enter the brain and force people to kill. Sam and Dean join forces with Bobby and Rufus and track it to a cannery, only to discover that Gwen and Samuel are also there looking for the monster... and none of them know who the monster is inside.