Hamsters can survive a course of clindamycin if they are held in a protected environment. Inoculation of Clostridium difficile regularly results in fatal enterocecitis in such animals but is without effect in untreated animals. These findings suggest that in the development of enterocecitis, clindamycin treatment and infection with C. difficile are separate events, and they imply that hamsters usually acquire C. difficile from environmental sources. Environments appear to differ in the risk of exposure to C. difficile, high-, medium-, and low-risk areas being recognizable. Once introduced, C. difficile may spread from animal to animal. Parallel with the incidence and epidemiology of human antibiotic-associated pseudomembranous colitis are discussed.