In Lusaka, where human immunodeficiency virus seroprevalence in young adults is approximately 25%, four townships were studied to establish the prevalence of persistent diarrhea in adults and the etiologic importance of cryptosporidiosis in adults with persistent diarrhea. Cryptosporidium parvum oocyst contamination of urban water supplies was measured and the results used to categorize these populations into high or low exposure. In total, 506 adults were reported as having had diarrhea in the 2 weeks prior to the survey; 101 of these episodes were persistent. Adults with persistent diarrhea in the high-exposure areas were more likely to have cryptosporidiosis (odds ratio, 5.14; 95% confidence interval, 1.57-17.2; risk ratio, 1.83; 95% confidence interval, 1.04-3.21; P = .003) although overall prevalence of persistent diarrhea was not greater in these areas. This association was not confounded by animal exposure, travel, or boiling water. Within these urban populations, water contamination with C. parvum was a major influence on the prevalence of infection.