The prevalence of circulating cytomegalic endothelial cells, detected currently by the pp65-antigenemia assay and described previously in blood of transplanted and AIDS patients with disseminated human cytomegalovirus (HCMV) infection, was found to be 2.9% in the AIDS population and 6.5% in the fraction of the AIDS population with HCMV in blood. Cytomegalic endothelial cells increased to 39.7% and 48.4%, respectively, in AIDS patients with very high levels of antigenemia and viremia, while an end organ disease reached an incidence of 76.4%. Positive and negative predictive values of cytomegalic endothelial cell detection for diagnosis of HCMV end organ disease were 73.1% and 21.4% with antigenemia levels >1,000, respectively. On the other hand, in a selected group of 38 cytomegalic endothelial cell-positive AIDS patients with <50 CD4+ T cells/μl and late-stage HCMV disease, who were followed-up for variable periods of time, the prevalence of high level antigenemia was 95.3%, that of viremia 86.0% and that of L-DNAemia 92.7%, while the incidence of HCMV end organ disease was 84.2%. In this population, it was shown that cytomegalic endothelial cell presence was associated with lack of (56.0% of episodes) or insufficient (4.0%) anti-HCMV treatment or emergence of HCMV drug-resistant strains (17.3%) or short-term response to antiviral treatment (22.7%); was determined in the same patient by different conditions during follow-up. Longitudinal observations indicated that cytomegalic endothelial cells were detected often in blood at least 3 months later than end organ disease suggesting that the duration of end organ disease was a cofactor associated with the appearance of cytomegalic endothelial cells. J. Med. Virol. 55:64–74, 1998. © 1998 Wiley-Liss, Inc.