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To compare the pathogenesis of human genotype 1 (HuGl) and bovine genotype 2 (BoG2) Cryptosporidium parvum, neonatal gnotobiotic pigs were given 1-10 HuGl or BoG2 oocysts. The prepatent and patent periods were significantly longer for HuGl than for BoG2 C. parvum (prepatent, 8.6 vs. 5.6 days; patent, 16.6 vs. 10.3 days). BoG2-infected pigs developed signif- icantly more severe disease than did HuGl-infected pigs. BoG2 parasites were seen micro- scopically throughout the intestines during the prepatent and patent periods. HuGl parasites were only detected during the patent period in the ileum and colon but colonized the mucosal surface in significantly larger numbers than did BoG2. Moderate-to-severe villus/mucosal attenuation with lymphoid hyperplasia was seen throughout the intestines of BoG2-infected pigs, whereas lesions in HuGl-infected pigs were mild to moderate and restricted to the ileum and colon. These findings provide additional support for the hypothesis that human and bovine C. parvum genotypes may be separate species.