Mycobacterium avium complex (MAC) is a common environmental organism. Disease in humans due to this organism is primarily manifested by three clinical syndromes: disseminated disease, usually in persons with advanced human immunodeficiency virus (HIV) infection; pulmonary disease, in persons whose systemic immunity is intact; and cervical lymphadenitis, also a disease of normal hosts. Disseminated disease in persons with AIDS is the most common clinical presentation, and all three syndromes are increasing in frequency. Research is needed to identify the environmental reservoirs and modes of acquisition leading to MAC disease in humans and to explain recent increases in occurrence.