The seroprevalence and incidence of Helicobacter pylori infection were determined among 312 North American missionaries who were serving in developing countries between 1967 and 1984. The majority (81%) resided in sub-Saharan Africa. When initially evaluated, the missionaries had a mean age of 40 years, 65% were female, and all were of white race/ethnicity. An ELISA showed that the initial prevalence of IgG antibody to H. pylori was 17%. After a mean of 7.4 years of service (1917 person-years of exposure), 37 (14%) of 259 initially seronegative subjects seroconverted to anti-H. pylori, giving an annual incidence of 1.9%. These data indicate a relatively higher risk of H. pylori infection among missionaries compared with an annual incidence of seroconversion of 0.3-1.0% in industrialized nations. Long-term residents in developing countries should be evaluated for H. pylori infection when gastrointestinal symptoms develop.