To determine if microbiologic cure of AIDS-related disseminated Mycobacterium avium complex (MAC) is possible in patients receiving highly active antiretroviral therapy (HAART), 4 patients with a history of disseminated MAC received ≥12 months of macrolide-based antimycobacterial therapy. All were asymptomatic and had absolute CD4 cell count >100/μL (range, 137-301) and <10,000 copies/mL of human immunodeficiency virus RNA (range, <500-1250). A bone marrow aspirate and peripheral blood were obtained for mycobacterial culture. Follow-up blood cultures were obtained routinely at 4 weeks and every 8 weeks thereafter. All 4 patients had negative bone marrow and blood cultures and then discontinued antimycobacterial therapy. All patients' subsequent cultures remain sterile and all are clinically asymptomatic (range, 8-13 months follow-up). It appears that disseminated MAC infection can be cured by prolonged antimycobacterial therapy in some persons who experience sustained CD4 lymphocyte increases while receiving HAART.