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We conducted a prospective case-control study to investigate the epidemiology, clinical features, and systemic antibody responses of cryptosporidiosis in Bangladeshi children. Forty-six children presenting to the International Center for Diarrheal Disease Research, Bangladesh in Dhaka, Bangladesh with diarrhea and Cryptosporidium spp. oocysts in the stool were enrolled as cases. Forty-six age-matched children with diarrhea, but without cryptosporidial infection, were enrolled as controls. Thirty cases and 23 controls returned for follow-up three weeks after discharge. Infection with Cryptosporidium spp. occurred most commonly in those less than two years of age, was accompanied by watery diarrhea and vomiting, and was more likely to be associated with persistent diarrhea. Other than duration of diarrhea, there were no significant differences in clinical or epidemiologic features between cases and controls. Cryptosporidium-specific serum IgM levels were significantly higher in cases compared with controls at presentation. In addition, there was a significant increase in serum Cryptosporidium-specific serum IgG levels over the three-week follow-up period in cases compared with controls. Within the case group, there was no difference between children with acute and persistent diarrhea in the change in IgG levels over the follow-up period. However, there was a significant difference between children with acute and persistent diarrhea in changes in both IgA and IgM levels, with persistent diarrhea being associated with a decrease in levels of both antibodies.