The role of an antigenemia assay in the diagnosis and prediction of human cytomegalovirus (HCMV) disease in AIDS patients was evaluated. The clinical history of 62 patients with advanced HIV infection from whom a total of 248 blood samples were drawn and tested by the HCMV antigenemia assay was examined retrospectively. Between December 1992 and January 1994, 28 episodes of HCMV disease with organ involvement were recorded; the antigenemia assay was positive in 23 of them (82.1%). In particular, this test was positive in 11 of 12 (91.6%) first episodes and in 3 of 3 (100%) recurrent episodes occurring in patients not receiving maintenance therapy. The same test was positive in 9 of 13 (69.2%) recurrent episodes occurring in patients receiving maintenance therapy. The first occurrence of HCMV disease was always preceded by a positive antigenemia assay 2 and 4 months before diagnosis (in all 7 patients of the 7 for whom a blood sample was available before HCMV disease). A positive antigenemia test result was not always followed by organ involvement, but a high positive cell count (> 100/200,000 polymorphonuclear leukocytes) strongly correlated with the appearance of HCMV disease in the following 1 to 3 months (100% of cases). The antigenemia assay is a useful and reliable indirect method for the diagnosis and prediction of HCMV end-organ disease in severely and persistently immunocompromised AIDS patients.