As Lou (Natasha Lyonne) stumbles out of her dilapidated trailer, the residue of last night’s festivities clings to her like a tattered blanket. Rural Michigan has not been kind lately; a series of disappearances has cast a shadow over the town, establishing an atmosphere thick with unease. Lou's discomfort is amplified by her very being, reflecting the unrest brewing in the community around her.
Her close friend Sadie (Chloë Sevigny) suspects Lou is concealing a significant secret - one that hints at a potential pregnancy. However, Lou is insistent, declaring that it has been nearly a year since she last had any intimate relations. Yet the truth is laced with complexity; a traumatic event from six months earlier — a miscarriage that occurred during a night out at a club — has left her feeling profoundly vulnerable and uneasy. As she prepares for her cleaning shift at the local motel, an oddball stranger named Lorna (Meg Tilly) checks into a room, her presence hanging in the air like a mysterious secret only Lou seems to perceive.
In the backdrop, Sadie’s boyfriend Gabriel (Mark Webber) wears many hats; he is a drug dealer, a pimp, and a keeper of murky secrets. His associate Warren, meanwhile, has been busy concocting unstable drugs that the unwitting locals have begun to sample, leading to disturbingly grotesque results – skin turning inside out as if performing a horrific ballet. Gabriel’s ulterior motive revolves around reuniting Sadie with her estranged child, a task he fears is perpetually out of reach. Caught within this tangled web of deceit and tension, Lou's life spirals as the fragile boundary between reality and nightmare begins to collapse.
As the day progresses, Lou's perception unravels. Amidst a metaphoric backdrop, she finds herself enveloped in hallucinatory visions populated by figures from Funzone, a local amusement center. Their somber expressions starkly contrast the usual lighthearted aura of the establishment as they conduct a clinical examination of her. Suddenly, the scene fades into darkness.
When Lou regains consciousness, she discovers a bloated stomach, akin to a balloon inflated by unseen hands. A strange blister appears on her foot, leaking a clear, viscous substance reminiscent of a slow-motion cascade – a captivating yet unsettling portent of the oddities soon to besiege her.
Lorna's entrance into Lou's life shakes things up even further. Claiming to be clairvoyant, Lorna perceives Lou's inner turmoil, having seen her during a previous encounter at the motel. Over a shared meal at Funzone, Lorna shares her harrowing backstory: a mysterious abduction during military service followed by her dismissal when she dared to question authority.
As the facts start to emerge like fluid from Lou's blister, Warren, an employee at Funzone, becomes the centerpiece of Lou’s inquiries. His revelations shatter Lou's understanding of her world: Gabriel has been trafficking at-risk women to a shadowy figure known only as Isaac in return for drugs. The weight of Lorna's traumatic history, marred by surgical scars – of implants and removals – paints a grim picture of the darkness lurking behind the scenes.
Just when it seems some clarity is forming, Sadie appears, insisting Lou seek medical help. However, Lou is adamant; she refuses to entertain notions of pregnancy. The trio’s visit to the abandoned locale of the fateful party serves to deepen the enigma. Through a fog of resurfaced memories, Lou recalls being dosed with an experimental hormone by Gabriel, who had sinister motives all along. Then came Sadie’s shocking disclosure: Gabriel had used Lou as a test subject for this hormonal drug, a wicked secret he had been peddling on the black market.
In Lou's humble home, Lorna embarks on an unusual mission to extract the disturbing growth protruding from Lou's midsection. Lou takes control, bringing forth a surreal and grotesque scene as she gives birth to a nightmarish, animate disembodied cranium that defies all comprehension. The chaos escalates with the arrival of Gabriel and Isaac, who are accompanied by a SWAT operative, resulting in Lorna’s tragic demise amidst a barrage of bullets.
The true essence of Isaac's intentions surfaces in the madness: he reveals a twisted goal to engineer a new breed of humanity capable of withstanding the harshness of outer space environment. Unbeknownst to her, Lou's tumultuous lifestyle, filled with reckless abandon, has inadvertently turned her into the ideal incubator for their dark experiment. Isaac proposes an alliance, hoping to recruit Lou in crafting this superior race, but she staunchly declines.
As Isaac elaborates on his chilling plan, surreal and bizarre phenomena unfold: limbs start to emerge unnaturally from Lou's body, and her skeletal structure gradually emerges, leaving behind an empty shell of flesh. The disembodied head Lou previously birthed suddenly springs to life, animating with an unexpected ferocity as it goes after Gabriel and Isaac, ultimately leading to their demise.
As a SWAT operative bursts into the scene, he’s met with a grotesque tableau – blood everywhere and a terrifying, fully-formed creature poised in the kitchen, clutching its own head in a haunting expression of despair.
