A forest-dwelling hermit discovers his dog has died from a mysterious illness and is sprayed by its infected blood. Five young friends, Paul, Karen, Bert, Jeff and Marcy have rented a cabin in the same woods for a week-long vacation. The group stops for supplies at Priddy's General Store. Dennis, the intellectually-disabled son of the store manager, unexpectedly bites Paul's hand.
At the cabin, Jeff and Marcy have sex, Paul and Karen share a kiss while sunbathing and Bert ventures into the woods with a rifle. Bert encounters and accidentally shoots the hermit. Though initially concerned, he panics when he realizes the hermit is infected with a disease and flees. He says nothing about the incident to his friends.
Later that evening, while the group hang out around a campfire, a stranger who calls himself Grim and his dog, Dr. Mambo, gatecrash their evening. The group seem very hesitant about letting him stay, but warm up to him after he shares marijuana with them.
Later that night, the infected hermit comes to the cabin in search of help. Bert slams the door in his face and the desperate man tries to steal the group's vehicle. A conflict ensues between the hermit and the five friends, during which they accidentally cripple their car and set fire to the hermit. He runs off into the woods, presumably to his death.
The next day, Jeff and Bert head out in search of help. They encounter a farmer who offers to help them, but hastily leave when they discover that the hermit is her cousin. Meanwhile, Deputy Winston arrives at the cabin to investigate reports of the previous night's commotion. Paul explains things without mentioning the hermit's presumed death. Winston promises to send a tow truck before departing.
Dr. Mambo returns to the cabin without Grim and seemingly infected. He threatens Paul and Bert, before Marcy scares him off with the rifle.
While Paul and Karen make out, they discover that Karen is infected with the flesh-eating virus and her leg has started to decay. Fearful of contagion, the others lock her in the shed. Paul leaves on foot to find help, but the only people he encounters chase him away, mistaking him for a peeping Tom.
The following morning, the group's attempt to evacuate is botched when Karen vomits blood all over the interior of the car. Bert drives back to the general store alone and Jeff abandons everybody and flees to a remote shack. Marcy and Paul lament their poor chances of surviving and make passionate love, believing they won't live long enough to regret it. They later discover marks on Marcy's back that reveal she, too, is sick.
At the general store, Dennis bites Bert's hand just as he did with Paul. His father, Tommy, lashes out at Bert for exposing his son to the virus, and he and his friends chase Bert down in order to contain the disease. While once again searching for help, Paul encounters the severely-burnt hermit in the lake. Surprisingly, he is still alive and he attacks Paul, only for Paul to fend him off and finally kill him.
Marcy draws a bath and shaves her legs, causing the infected flesh to gruesomely peel from her body. She stumbles outside in distress and is mauled to death by Dr. Mambo.
Paul returns to the boat shed where Karen begs him to kill her. His gun is empty and since he's unable to finish the job of splitting her face with a shovel, Paul sets the shed on fire and watches in horror as Karen is completely burned alive. Bert makes it back to the cabin, but he is followed and shot dead by Tommy. Paul recovers Bert's rifle and guns down Tommy and his two accomplices. Paul escapes in Tommy's truck, but crashes it into a tree and explodes. Covered in blood, Paul stumbles upon a small campfire party attended by Deputy Winston. Winston receives a radio call from the sheriff ordering her to shoot Paul on sight. However, Paul convinces Winston to let him go instead.
The next morning, Jeff returns to the cabin. He finds his friends' corpses, but rejoices in having survived the ordeal himself. He's then gunned down by Deputy Winston. Paul succumbs to infection and drops dead in the woods. Dennis discovers his corpse. Back at the cabin, authorities and a hazmat crew clean up the scene.
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