To establish the diagnostic value of the cytomegalovirus (CMV)-pp65 antigenemia in CMV disease occurring in human immunodeficiency (HIV)-infected patients, CMV-pp65 antigen in polymorphonuclear leukocytes (PMNLs) was assayed in 373 samples from 138 randomly included patients followed up for symptomatic HIV-1 infection and the correlation between CMV-pp65 antigenemia and diagnosis of CMV disease was investigated. Thirty-seven CMV disease episodes were observed in 30 patients and 89.2% of these episodes were associated with a positive CMV-pp65 antigenemia. In contrast, 94% of the patients negative for CMV-pp65 antigenemia remained free of CMV disease. Patients with CMV disease had significantly higher levels of CMV-pp65 antigenemia than CMV disease-free patients (695 positive cells/2 x 10(5) PMNLs vs. 28 positive cells/2 x 10(5) PMNLs). The positive and negative predictive values of the test were 45% and 94%, respectively, but were 93% and 80%, respectively, when a CMV-pp65 antigenemia level of > 100 positive cells/2 x 10(5) PMNLs was taken into consideration. These results indicate that the CMV-pp65 antigenemia assay is useful for the diagnosis and monitoring of CMV disease in HIV-infected patients.