A prospective study of US Peace Corps volunteers (PCVs) serving in Zaire, central Africa, was undertaken to determine the risk of human immunodeficiency virus (HIV) and hepatitis B virus infection in an acquired immunodeficiency syndrome-aware expatriate population living in an area of high endemicity for both diseases. Of the 338 PCVs who served in Zaire between October 1985 and May 1988, 282 (83%) were enrolled, representing 7776 volunteer-months of service. Analyses of serum samples for HIV and hepatitis B virus were performed on enrollment and at completion of service. All PCVs received extensive education and counseling regarding HIV and acquired immunodeficiency syndrome throughout their stay in Zaire. There were no documented seroconversions to HIV among 282 PCVs who lived in Zaire for periods ranging from 1 to 81 months, with a mean length of stay of 27.4 months. Of the 14 (6.2%) of 226 PCVs tested who had at least one positive serologic marker for infection with hepatitis B virus, none was documented to have seroconverted during service. During the study period, the rate of all sexually transmitted diseases among PCVs in Africa decreased from 131 to 68 per 1000 study population per year, and there were 52 cases of confirmed malaria among volunteers in Zaire. These data suggest that the risk of acquiring infection with HIV or hepatitis B virus in PCVs in Zaire is very low, and there is no evidence for unusual modes of transmission.