During a 4-month period, 31 of 156 ferrets (Mustela putorius) in a biomedical research program developed protracted diarrhea. Clinical signs were green mucohemorrhagic fecal material, partially prolapsed rectum, anorexia, body weight loss, and dehydration. Nine of the affected animals were necropsied. On gross examination, the descending colon was grossly thick and histologically characterized by marked proliferation of the mucosa, relatively few goblet cells, mixed inflammatory cell infiltrate, and penetration of the mucosal glands through the muscularis mucosa into the submucosa and tunica muscularis. Campylobacter fetus subsp jejuni was isolated from 6 of 9 ferrets with proliferative colitis. Warthin-Starry stained sections of hyperplastic colon revealed large numbers of organisms in the apical portion of epithelial cells, and organisms similar to Campylobacter spp were observed by electron microscopy in hyperplastic colonic epithelium. The proliferative colitis in the ferret is compared with the pathologic and bacterial features of similar intestinal proliferative diseases in swine and hamsters.