Mycobacterium avium complex (MAC) in simian immunodeficiency virus (SIV)-infected macaques is a frequent opportunistic infection that shares many features with the condition in human AIDS patients. A retrospective analysis of necropsies on 135 macaques with SIV-induced simian AIDS that received neither antiretroviral nor antimicrobial therapy revealed that 17% (23/135) were infected with MAC. MAC developed in 31.3% (21/67) of the animals inoculated with uncloned SIVmac251 versus 1.9% (1/53) and 6.7% (1/15) of the animals inoculated with the molecular clones SIVmac239 and SIVmac239/316EM, respectively (P = .001). This is the first example in which the risk of infection with a specific opportunistic organism was affected by the infecting strain of immunodeficiency virus. In addition, animals with MAC had a longer mean survival after primary infection and lower CD4 cell counts at death than animals that did not develop this opportunistic infection. The SIV-inoculated macaque is a valuable model in which to study the pathogenesis of MAC in the immunocompromised host.