Although the pathogenicity of Blastocystis hominis has been extensively debated in the medical literature, controlled studies of the association between B. hominis and diarrhea are lacking. We conducted a case-control study among expatriates and tourists in Kathmandu, Nepal, in which we compared the prevalence of the organism among patients with diarrhea to that among a control group without diarrhea. B. hominis was detected in 56 (30%) of 189 patients with diarrhea, compared with 40 (36%) of 112 asymptomatic controls. Patients with diarrhea were significantly more likely to have > or = 10 B. hominis organisms per high-power (400x) field than were controls. However, among the 25 patients with this concentration of organisms, other enteric pathogens were detected in 17 (68%). Only 8 (4%) of 189 patients with diarrhea had > or = 10 B. hominis organisms per high-power field detected in the absence of other pathogens, compared with 5 (5%) of 112 asymptomatic controls. Thus, B. hominis in higher concentrations was not associated with diarrhea. There were no specific symptoms associated with B. hominis infection, and the presence of higher concentrations of the organism in stool was not associated with more-severe symptoms. Despite the high prevalence of the organism among travelers and expatriates in Nepal, the results of this study suggest that B. hominis does not cause diarrhea in this population.