Between November 1997 and April 20, 1998, bloody diarrhea sickened 298 persons in Cameroon. Laboratory investigation of the epidemic (case-fatality rate, 16.4%) documented amoebiasis in one of three patients and three types of pathogens: multidrug-resistant Shigella dysenteriae type 1, S. boydii, and enterohemorrhagic Escherichia coli. We report the first isolation of E. coli O157:H7 in Cameroon and the second series of cases in the Central African region.