Rowf, a shaggy black mongrel, and Snitter, a black-and-white fox terrier, are among dozens of animals being cruelly held in a testing facility in North West England. When one of the handlers fails to close Rowf's cage properly, the two dogs make a daring escape into the English countryside, where they befriend a red fox who helps them survive in the wild.

But as rumors circulate that the dogs may have been the test subjects for biological weapons and could be carrying a terrible plague, they soon find themselves targets of a great dog hunt. Local farmers, politicians, scientists, and even the military join in the search to track them down.