In humans infected with the human immunodeficiency virus (HIV), clinical disease due to human cytomegalovirus (HCMV) infection is one of the AIDS-defining diseases; HCMV is the most common opportunistic infection found postmortem. Histologically, the typical lesions are characterized by "owl's eye cells." In rhesus monkeys infected with simian immunodeficiency virus (SIV), comparable lesions are caused by an infection with the rhesus CMV (RhCMV). The aim of this study was to investigate the incidence of productive and latent RhCMV infection in monkeys infected with SIV macaques (SIVmac). Eleven SIVmac-infected rhesus monkeys, which were euthanatized after developing AIDS-like disease, and 11 clinically healthy and uninfected animals comprised the study. The monkeys were screened serologically for RhCMV by western-blot analysis. Immunohistochemistry was performed by an indirect immunoperoxidase technique with a polyclonal rabbit RhCMV-antiserum. Lesions characteristic of RhCMV-associated diseases were detected histologically. All animals were latently RhCMV-infected. Seven of eleven (63.6%) SIV-infected macaques were productively RhCMV infected according to immunohistochemistry. RhCMV antigen was identified in the gastrointestinal tract, the hepatobiliary system, the lungs, and the testicles. Two of these seven animals showed characteristic inflammatory lesions associated with productive infection. Consequently, the CMV prevalence in SIVmac-infected rhesus monkeys and human AIDS patients is comparable.