A syndrome of acquired immunodeficiency has been identified in a group of rhesus monkeys (Macaca mulatta) which died at the California Primate Research Center. Clinical evaluation of these animals revealed that 50% or more had lymphadenopathy, weight loss, and diarrhea. At least 30% had splenomegaly, fever, cutaneous abscesses and/or arthritis/myositis. Two animals had fibrosarcomas. Anemia was seen in 19 animals, lymphopenia in 14, granulocytopenia in four and thrombocytopenia in three. Hepatitis was diagnosed histopathologically in 13. Electrophoresis revealed hypoproteinemia, hypoalbuminemia and hypogammaglobulinemia. Numerous bacterial, protozoal, and viral agents were identified including cytomegalovirus and leukocyte-associated herpesvirus. Pathologic lesions included severe post-reactive depletion of lymphocytes in germinal centers and paracortical regions of lymph nodes. Clinical and pathologic changes indicate an acquired immunodeficiency syndrome which has some similarities to AIDS in humans. This disease in monkeys may provide a model for studying that disease.