Despite the recognition of Mycobacterium avium complex (MAC) infection as a common complication of AIDS, the specific clinical features, significance, and need for treatment have been difficult to assess. We reviewed the clinical records and autopsy material of 68 patients dying with AIDS, 32 (47 percent) of whom had MAC isolated from autopsy tissue. All had postmortem evidence of systemic infection. Eleven (34 percent) had MAC isolated from lung tissue. Little, if any, local tissue inflammation and destruction were associated with MAC infection. Patients with autopsy evidence of MAC infection had a longer time interval from diagnosis of AIDS to death. The infection was detected antemortem in 14 (44 percent), blood culture being the most sensitive means (86 percent yield). Although recurrent fever was noted among both MAC infected and uninfected patients, weight loss greater than 20 lb, weakness, anorexia, abdominal pain, and diarrhea were more frequent among infected patients. Severe anemia, thrombocytopenia, lymphopenia, and reduced mean CD-4 percentages and CD-4/CD-8 ratios were associated with MAC infection. Of eight patients who had MAC cultured antemortem and received multidrug antituberculosis therapy, none responded clinically, and all but one had MAC isolated at autopsy. Because MAC is associated with significant discomfort and disability, development of more effective treatment regimens could be beneficial for some affected AIDS patients.