LP-BM5 murine leukemia virus infection caused alterations in splenic T cell subsets in adult C57BL/6 female mice. Prolonged infection resulted in increased immunosuppression and a concomitant decreased resistance to Cryptosporidium parvum infection. Significant Cryptosporidium colonization of the intestinal villi was seen 10 days after oral challenge in mice infected with murine retrovirus for 3 months but not in non-virally infected controls. Parasite numbers per villus of retrovirally infected mice were 20-fold higher than in controls, which showed only occasional parasites. Feces from most virally infected mice but none from controls contained oocysts. Cryptosporidium infection in mice after 4 and 5 months of retroviral infection was accompanied by severe immunosuppression and parasite levels 50-5000 times higher than in controls. A high level of infection persisted 21 days after Cryptosporidium challenge in virally infected mice, while controls cleared their transient and marginal infection. These results further characterize LP-BM5 infection as a murine model of retrovirally induced acquired immune deficiency.