Two to 5 days after oral inoculation with Cryptosporidium obtained from infected calves, 7 newborn specific-pathogen-free lambs became depressed and anorectic and developed diarrhea. Four moribund lambs were killed within 3 days after onset of illness, and the 3 other lambs died after protracted intermittent diarrhea and reduced milk intake, which lasted up to 14 days. The small and large intestines were heavily infected with Cryptosporidium, with the terminal portion of the ileum being the most severely affected. Histologic examination revealed villous atrophy, with considerable fusion and epithelial cross-bridging between villi. Lambs infected at 5 to 20 days of age had less severe clinical signs of disease, with intermittent diarrhea, reduced milk intake, and growth retardation. Lambs infected at 30 days of age became infected with the organism, but did not develop clinical signs of disease or growth retardation.