Protestant missionaries (n = 360) serving in sub-Saharan Africa between 1967–1984 were studied to determine the risk of hepatitis A virus (HAV) and hepatitis B virus (HBV) infection. Personnel were serologically screened for antibody to both the hepatitis A virus (anti-HAV) and the surface antigen to the hepatitis B virus (anti-HBs) prior to departure, periodically during service abroad, and upon completion of their African tour. Rates of seroconversion were used as measures of the incidence of infection. Prior to service, 16% of the staff had anti-HAV and 3% had anti-HBs; post-service rates were 42% and 26%, respectively. Over 90% of the staff with > 20 years of service were seropositive for anti-HAV. For both viruses, the infection rate was highest during the first 1–2 years of service, when 28% of those susceptible to HAV and 11% of those susceptible to HBV became infected. Over the next decade, the median annual attack rate was 5.4% for HAV and 4.2% for HBV. Differences in the missionary HBV infection rate among the various African nations served tended to reflect differences in the magnitude of chronic HBV carriage among indigenous population groups. We conclude that missionaries to sub-Saharan Africa are at enhanced risk of both HAV and HBV infection, and that all should receive passive immunization with immune globulin and active immunization with hepatitis B vaccine.