Although numerous studies have shown that diarrhea is the most common illness occurring during the first few weeks of travel, systematic studies of the incidence of diarrhea during long-term residence in developing countries have not been performed. We conducted a cohort study of the incidence and etiology of diarrhea among 77 expatriate adults who had lived in Nepal for <2 years. Persons were followed prospectively for up to 1 year (mean, 9 months). The incidence of diarrhea during the surveillance period was 3.3 episodes of diarrhea per person per year, or 0.27 episodes per person per month. The annual attack rate of specific pathogens was 42% for enterotoxigenic Escherichia coli, 32% for Cyclospora species, 16% for Giardia lamblia, 16% for Shigella species, 10% for Campylobacter species, > or =10% for rotavirus, and 6% for Entamoeba histolytica. This study suggests that adult persons from developed countries who move to developing countries such as Nepal remain at high risk for diarrhea during their first 2 years of residence.