The aim of the present study was to evaluate the usefulness of the Digene Hybrid Capture System (DHCS) for the detection and quantitation of cytomegalovirus (CMV) DNA in 95 blood samples from 57 HIV-positive patients with low CD4+ T-cell count (<100 cells/ l). The DHCS was compared with pp65 antigenemia assay and the results were correlated with active CMV disease, anti-CMV therapy and occurrence of disease relapses. Our data suggest that the detection of CMV DNA by DHCS seems to be a rapid, sensitive and specific assay for the diagnosis of CMV disease in HIV-infected patients, showing a good correlation with pp65 antigenemia assay. Overall, the DHCS provides a quantitative and objective measure of CMV activity in leukocytes and it may also represent a useful tool for the monitoring of anti-CMV therapy.