Chronic cryptosporidiosis is a common opportunistic infection in humans with AIDS and also in macaques with SIV-induced immunodeficiency. Cryptosporidiosis in SIV infected macaques is being evaluated as an animal model system for studying pathogenesis of cryptosporidium in immune compromised hosts, and for testing the efficacy of therapeutic interventions. Ten SIV-infected rhesus macaques, released from other SIV research projects have been enrolled in the study. Baseline data on clinical and immunologic status have been collected for "staging" of SIV-related disease. To date, four animals with CD4 cell counts above 250/ul and free of naturally acquired cryptosporidiosis have been inoculated orally with infectious oocysts, two with a dose of 100 oocysts and two with 1000 oocysts. Intermittent, low level shedding of oocysts has been observed in all 4 animals without diarrhea these animals showed no "boost" in serum IGG or in vitro lymphocyte proliferation against oocysts antigens. Analyses of saliva and gut lavage samples for cryptosporidium-specific IGA responses are in progress. Techniques have been established to harvest gut mucosal lymphocytes for immunologic analyses. In addition, two animals have been identified with naturally acquired cryptosporidium infection that are chronic shedders of oocysts, without clinical disease. Analysis of the cryptosporidium-specific immune responses of these animals is in progress.