Rowf, a labrador-mix, and Snitter, a smooth fox-terrier, are two of many dogs used for experiments at an animal research facility in the Lake District of north-western England. Snitter has endured brain surgery—leaving the top of his head scarred and covered with bandages—while Rowf has been drowned and resuscitated repeatedly.
One evening, Snitter slips under the netting of his cage and into Rowf's, and the two discover that Rowf's cage is unlatched. They slip into each other’s spaces and explore the facility, seeking any chance to escape, until they reach the incinerator and come alarmingly close to being killed before finally breaking free.
At first, freedom feels sweet and full of possibility, but the dogs soon confront the harsher realities of life in the wild. They must navigate the dangers of a landscape that now treats them as fugitives, all while realizing they are being hunted by their former captors. In time, they form an uneasy alliance with the Tod, a nameless Geordie-accented fox who goes by the local slang for a wild fox. The Tod teaches them to hunt and survive, demanding a share of their kills in return for his know‑how.
Snitter clings to the hope of finding a new home, something he once had with a master, but tragedy strikes when he accidentally steps onto the trigger of a shotgun and, as he climbs onto a man, kills him. The accident deepens the heartbreak of their tenuous freedom and foreshadows the fragility of their lives on the run.
As weeks slip by, the two dogs grow gaunt and lean from starvation, resorting to stealing more food while trying to stay ahead of humans. The Tod proves to be a difficult partner, capable of acts that undermine their plans, such as when he hoards a nest of eggs for himself, angering Rowf. The Tod also disapproves of their riskier choices, like pursuing meals from sheep grazing on the local hills. The trio parts for a time, but the Tod eventually returns to help, distracting a lab-hired gunman long enough for the others to slip away, only for the gunman to fall to his death.
The relationship among the three dogs eventually heals as they wander together, with rumors spreading that a 3rd Battalion Parachute Regiment and the media are chasing them, driven by fears that the dogs may carry bubonic plague or harm people and livestock. The Tod finally guides them to a train pulled by the River Irt on the Ravenglass and Eskdale Railway, and in a final act of sacrifice, he diverts attention away from Snitter and Rowf, allowing them to escape as gunmen close in.
Their path leads them to Ravenglass, but once they disembark the train, they are spotted by an RAF Sea King helicopter and press on toward the shoreline, where they reach a point of no return. Meanwhile, the research facility receives a call from a minister demanding an end to all experiments, adding political pressure to the human pursuit.
As armed troops close in, Snitter looks toward the water and says he can see an island. He dives in and begins to swim, followed by Rowf, whose conditioned fear of water is overwhelmed by a deeper fear of the gunmen. Two shots ring out, but the bullets seem to miss; a white mist envelops both dogs, and the helicopter and humans vanish from view. They swim toward the apparition of an island, with Snitter insisting that it exists even as he grows uncertain. Rowf presses on, certain he sees the island and urging his companion to keep swimming. When the mist finally lifts at the end, it reveals an island on the distant horizon—a possible refuge beyond the reach of those who chase them.