To study the pathogenesis of Mycobacterium avium complex (MAC) bacteremia, the extent of organ involvement was determined in a retrospective cohort of 44 AIDS patients with MAC bacteremia and complete autopsies between 1988 and 1992. Clinical and microbiologic histories were reviewed and lymph nodes, spleen, liver, bone marrow, small intestine, and colon from each autopsy were systematically evaluated for the presence of mycobacteria or foamy histiocytes. Of the patients, 30% had no histologic evidence of MAC. In the remaining 70%, reticuloendothelial and gastrointestinal involvement was most common, but the number and distribution of involved sites was highly variable. The risk of developing detectable histologic involvement was related to the duration of bacteremia. In contrast to the prevailing concept, our data suggest that MAC bacteremia may precede widespread tissue disease.