A lonely waitress with a tragic past, Agnes (Ashley Judd) rents a room in a run-down motel, living in fear of her abusive, recently paroled ex-husband (Harry Connick, Jr). But when Agnes begins a tentative romance with Peter (Michael Shannon), an eccentric, nervous drifter, she starts to feel hopeful again.

But Peter starts to imagine some horrific presence; he believes there is an infestation of bugs but Agnes can't see anything. As Peter's visions of bugs get more intense he starts to believe that they are crawling under his skin. Agnes will either have to convince Peter he is deluded or face up to the possibility that they may be the victims of a twisted government experiment.