The seroprevalence and incidence of hepatitis A, B, C, and E virus infection were determined among North American missionaries (n = 328) serving in various geographic locations between 1967 and 1984. The mean age of subjects at entry into the study was 39.7 years (range 5-73 years); 65% were female: 89% had lived outside the United States before the study began. Seventy-eight percent of subjects served in sub-Saharan Africa during the study. At initial evaluation, 50.9% of the subjects had antibodies to hepatitis A virus (total anti-HAV), 8.5% to hepatitis B virus core antigen (total anti-HBc), 0.6% to hepatitis C virus (total anti-HCV by second- generation immunoblot assay), and 0% to hepatitis E virus (IgG anti-HEV). After an average period of service of 7.3 years (2,396 person-years total), 5.8% of the missionaries seroconverted to anti-HAV, 5.5% to anti-HBc, 0.6% to anti-HCV, and 0% to anti-HEV. This study indicates a relatively low risk of hepatitis C and E virus infection among missionaries while confirming the previously reported high risk of hepatitis A and B virus infection. Hepatitis A and B vaccination is recommended for long-term travelers to developing countries.