The pathology of disseminated Mycobacterium avium-intracellulare (MAI) was studied in 20 specimens from 11 patients. The patients ranged from 28 to 65 years and included 8 immunosuppressed and 3 immunocompetent hosts. Specimens of lymph node (five), spleen (one), liver (four), bone (three), pulmonary tissue (three), skin (three), and an aortic aneurysm were included. All cultured specimens grew MAI, but only two-thirds of these showed acid-fast bacilli (AFB) on staining. Some tissues (liver, spleen) showed granulomas similar to those seen in tuberculosis. Other tissues (skin, bone, bronchus) showed necrotizing acute and chronic inflammation with histiocytes but no definite granulomas. Lymph nodes showed a variety of nonnecrotizing and necrotizing granulomatous lesions. In skin, bone, and some lymph nodes, MAI infection appears to be histopathologically distinguishable from tuberculosis. The cases reported here are distinct from those reported in some children and patients with the acquired immunodeficiency syndrome who have massive histiocytic infiltrates with innumerable intracellular AFB. This difference may be due to a specific defect in host response involving T-cell macrophage interaction.