Antibody titers to rhesus cytomegalovirus (RhCMV) were prospectively analyzed over a period of 68 weeks in a longitudinal serosurvey of 17 RhCMV-seropositive rhesus macaques (Macaca mulatta) experimentally coinfected with simian immunodeficiency virus (SIV). These were compared with anti-RhCMV titers in 18 animals that were also naturally infected with RhCMV but not infected with SIV. Fluctuations in anti-RhCMV antibody titers were observed within 5 weeks of SIV inoculation, and two distinct patterns of RhCMV antibody response were observed in SIV-infected animals. Animals showing a progressive decline in anti-RhCMV immunoglobulin G (IgG) exhibited the most rapid disease progression, coincident with low anti-SIV and anti-tetanus toxoid IgG responses, high levels of p27 antigen in the plasma, and short survival. Animals exhibiting a more stable CMV-specific response after SIV inoculation had the least rapid disease course. Anti-RhCMV antibody titers in SIV-uninfected animals remained relatively stable during the period of study. Evidence that preinoculation immunologic measures predicted postinoculation outcome was equivocal.