In an abandoned warehouse, a tortured Samandriel wills a spike to push its way out of his skull, allowing him to briefly summon Naomi for help. His efforts are interrupted however by a mysterious bow-tied demon doctor named Viggo, who menacingly places the spike back in his brain.
Back in Texas, Dean visits Sams hotel room to apologize for misleading him about Amelias safety, but Dean insists he was right about Bennys innocence. Unsure how to resolve their current stalemate, the brothers part ways for the moment. Elsewhere, Castiel is summoned before Naomi, and given instructions to rescue Samandriel, before having his memories blanked again.
Castiel recruits Dean for the effort to Hastings, Nebraska, while Sam finds himself confronted again by Amelia at his hotel door. Sam apologizes for returning to her life, however briefly, and offers to get out of her way before the two rekindle their passion with a kiss. Meanwhile, Viggo continues to inflict pain on Samandriel, stumbling upon a torture with skull-embedded pins that forces Samandriel to involuntarily chant in Enochian, setting fire to a local town bush.
Dean and Cas pay a visit to a man hospitalized by the burning bush, who reveals that he heard it speaking a strange language. Castiel surmises that the effects of an angels scream would cause such phenomena, giving them a direction to search. Back at the hotel, Sam and Amelia resolve not to repeat their mistake, but rather take some time to think about things, and meet back at the hotel in two days time if both want to resume their relationship.
Dean and Cas finally find the factory likely to hold Samandriel, but its demon guards would prove too much to handle. Instead, Castiel zaps them over to a freighter holding a disheveled Kevin, who has spent weeks translating his half of the tablet to no avail. Castiel leaves to gather materials for more of Kevins demon-incinerating bombs, while Dean fields a call from a distressed and wagon-slipping Benny, whom he cant help at the moment.
Crowley visits the factory at Viggos insistence, and realizes that Samandriels involuntary chants are kind of factory settings for angels, which may contain secrets the angels themselves dont consciously know. Back on the freighter, Castiel returns with the necessary materials as well as Sam, asking the brothers to stow their crap for the moment.
Sam, Dean and Castiel approach the factory at night, Castiel for the moment unable to enter due to the presence of angel sigils. Sam and Dean fight their way inside, defeating demons and destroying sigils, all the while Crowley races to uncover any useful information from Samandriels words. The boys manage to make it to the final door, but Samandriels torture begins to have a strange effect on Cas, giving him visions of Naomi and reducing him to a cowering whimper. Inside, Crowley finally learns from Samandriel of the existence of an angel tablet, much like the one designed to banish demons to hell.
The boys finally make it through the door, and kill the remaining demons as Castiel revives and frees Samandriel, taking him outside. Samandriel refuses to return to heaven, his knowledge of the tablet and the mysterious Naomi now awakened, as Naomi herself exerts her influence over Castiel. Despite his unconscious objections, Castiel does as Naomi orders and kills Samandriel for talking, telling Sam and Dean he had to do it out of self-defense. The brothers sense something wrong with Castiel given his eerily calm demeanor and bleeding eye, but the angel departs to return Samandriels body to heaven.
Later, after angel-proofing the cabin, Sam and Dean wonder aloud what could have caused Castiels strange behavior. With no leads, the brothers make up about Amelia, and Sam goes for a walk to determine what he should do. Dean finally calls back Benny, who remains kill-free for the moment, but Dean informs his vampire pal they shouldnt keep in contact anymore.
Finally, Amelia shows up to Sams motel room, only to find it empty, as the two brothers recline in their cabin and watch TV together over beers.