Hamsters developed scrapie 100-160 days after eating either scrapie-infected hamsters or infected brain. The clinical signs and neuropathology of scrapie transmitted by cannibalism were identical to those observed after intracerebral or intraperitoneal inoculation of the agent. Oral transmission of scrapie appears to be extremely inefficient. Cannibalism requires a dose of the scrapie agent of approximately 10(9) times greater than that needed to produce the disease by intracerebral injection for comparable periods of incubation. These results provide compelling evidence for oral transmission of scrapie and may offer new insights into the spread of kuru by cannibalism among the Fore people and their neighbors. The extreme inefficiency of oral infection with scrapie might also have implications for understanding the sporadic occurrence and worldwide distribution of Creutzfeldt-Jakob disease.