An outbreak of dysentery began late in 1979 in Central Africa and spread to involve a major portion of Zaire as well as Rwanda and Burundi. We traveled to a mission hospital in northeast Zaire during the epidemic and isolated Shigella dysenteriae, type 1, from most of the patients studied. All isolates were resistant to ampicillin, tetracycline, chloramphenicol, sulfathiazole, and streptomycin but sensitive to trimethoprim-sulfamethoxazole. Antimicrobial resistance was transferable to Escherichia coli, and at least three plasmids were identified in the donor Shigella isolates by using agarose gel electrophoresis. One was coded for ampicillin, tetracycline, and chloramphenicol resistance while a second conferred resistance to ampicillin and chloramphenicol but not tetracycline. A third large plasmid of approximately 120 megadaltons could not be transferred to E. coli recipients. All S. dysenteriae isolates yielded identical kinetic growth curves when analyzed on the Abbot MS-2 Research System. This is the most extensive outbreak of dysentery caused by S. dysenteriae reported since the Central American epidemic of 1969, and the first epidemic caused by a strain resistant to ampicillin.