A syndrome of acquired immunodeficiency within a group of outdoor-housed rhesus macaques (Macaca mulatta) with unusually high mortality has been identified at the California Primate Research Center. The cause of death for most of the affected animals included septicemia and/or chronic diarrhea with wasting, often complicated by other problems. In many cases, multiple or unusual infectious agents were isolated or recognized, including cytomegalovirus, Cryptosporidium spp., and Candida albicans. Septicemias due to usually innocuous agents such as Staphylococcus epidermidis and Alcaligenes faecalis were seen. Two animals developed cutaneous fibrosarcomas. Affected animals had generalized lymphadenopathy and splenomegaly, with depletion of T-cell populations, initially follicular hyperplasia followed by depletion, and absence of plasma cells. This spontaneous disease syndrome in nonhuman primates has similarities to acquired immune deficiency syndrome (AIDS) in humans, providing an animal model for the study of the complex factors modulating the immune system.