We retrospectively evaluated the role of pp65 antigenemia (AGM) as a marker of cytomegalovirus (CMV) disease and mortality in 241 HIV-infected patients with fever. Of 225 patients in whom CD4 count was available, 189 (84%) had counts below 100/microL and 209 (92.8%) below 200/microL, 149 patients had negative AGM (AGM-) and 92 had positive AGM (AGM+), AGM+ patients were at a more advanced stage of HIV disease, as evaluated by CD4 count (p < 0.001) and prior AIDS diagnosis (p < 0.001). Overall, 29 patients (12%) presented concomitant CMV disease (18 retinitis): 24 (26%) in the AGM+ group and 5 (3.3%) in the AGM- group (p < 0.001). AGM had a negative predictive value of 96.6% but a positive predictive value of 26% which increased to 65% if a cut-off of > 10 CMV-positive cells/10(5) leukocytes was considered. The cumulative rate of future CMV disease at 3 months was 0% in AGM patients, 3% in patients with AGM 1-10/10(5) and 36% in patients with AGM > 10/10(5). In a multivariate analysis, no antiretroviral therapy, AGM+ and CMV disease were independently associated with mortality. The role of AGM as a marker of present CMV disease is limited. However, quantitative AGM may select patients at a high risk of future CMV disease. In addition, AGM may be a marker of shorter survival in severely immunosuppressed HIV-infected patients.