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During the 2001 epidemic of foot and mouth disease (FMD) in livestock in England and Wales, we discovered a corresponding decrease in laboratory reports of cryptosporidiosis in humans. Using a regression model of laboratory reports of cryptosporidiosis, we found an estimated 35% (95% confidence interval [CI] 20% to 47%) reduction in reports during the weeks spanning the period from the first and last cases of FMD. The largest reduction occurred in northwest England, where the estimated decrease was 63% (95% CI 31% to 80%). Genotyping a subgroup of human isolates suggested that the proportion of Cryptosporidium genotype 2 strain (animal and human) was lower during the weeks of the FMD epidemic in 2001 compared with the same weeks in 2000. Our observations are consistent with livestock making a substantial contribution to Cryptosporidium infection in humans in England and Wales; our findings have implications for agriculture, visitors to rural areas, water companies, and regulators.