When the bad boy John inherits an isolated house in an island, he invites his brother and student of veterinary Matt and his girlfriend Nikki together with their common friends Sara and Noah to fly with him in his hydroplane and spend a couple of days having good time in the place. Later Sara is attacked by a dog and they recall that in the other side of the island there was a facility for training dogs that had been shutdown to avoid a rabies outbreak. While walking through the woods, they find a man called Luke, who sailed with his girlfriend Jenny to the island, covered of blood and Luke is killed by a pack of hounds. The group runs to the house and the animals put the place under siege, and they try to find a means of escape. When the survivors reach the compound, they disclose that the dogs have been genetically redesigned to become a breed of killers.

Kevin Smith interacts in Q&A sessions throughout various college stops in the USA.