Cryptosporidiosis was diagnosed in guinea-pigs, bred by a commercial labortory supplier, on histological examination of the intestine. Oral transmission to laboratory guinea-pigs aged up to 16 wk and to infant mice, with gut contents containing oocysts, was successful, but the organism failed to infect adult mice. From day 5 post-inoculation (pi) in guinea-pigs, infection of the ileum was associated with villous stunting and fusion, and with infiltrates of macrophages and other mononuclear cells, and eosinophils. Some guinea-pigs died; others were depressed and anorectic, with diarrhea or watery cecal contents. Mouse infections were subclinical, and caused no significant pathological changes. A bovine Cryptosporidium isolate infected infant mice but failed to infect young guinea-pigs. Guinea-pigs and infant mice excreted oocysts in feces after a prepatent period of 3-4 days. Some guinea-pigs excreted oocysts for up to 2 wk, but excretion in mice lasted only .apprx. 4 days. Infection of guinea-pigs by contact with a contaminated environment occurred with excretion of oocysts between 17-27 days after exposure. An indirect fluorescent antibody test (IFA) showed that antibody was present by day 17 pi with infected bowel contents, but none was detected in the guinea-pigs exposed to the contaminated environment. The IFA test demonstrated a serological relationship between the guinea-pig isolate and a bovine strain used to infect gnotobiotic lambs. Transmission electron microscopy of intestine from infected guinea-pigs and mice showed that > 1 schizont generation occurred. The 1st consisted of 8 merozoite packets attached to enterocytes, but many packets of 2 or 4 merozoites of the 2nd or subsequent generations were apparently released into the gut lumen. Fixed microgametocytes contained lipid vacuoles and had microneme-like structures in their cytoplasm. Oocysts and sporocyts were also identified, with sporulation occurring with the parasitiphorous vacuole. A sparse infection was established in 1 of 2 specific pathogen-free lambs (12-day-old) by day 3 pi, but no oocysts were detected in its cecal contents or in those of a 2nd lamb killed 4 days later.