The role of the major histocompatibility complex (MHC) in the pathogenesis of AIDS is complex because of compounding variables within the virus, host, and environment. Important variables can be controlled by using the experimental animal model of AIDS induced by simian immunodeficiency virus in rhesus monkeys (Macaca mulatta). We studied whether the MHC type influenced which opportunistic infections arose in an individual monkey. Several associations were found. For example, cytomegalovirus was strongly associated with Mamu-B6 (p < 0.001), whereas Cryptosporidium was associated strongly with Mamu-DR3 (p < 0.001). We also found that having one opportunistic infection increased the risk of having another.