Human cytomegalovirus (HCMV) replication in peripheral blood polymorphonuclear (PMNL) and mononuclear (MNL) leukocytes was investigated by quantitative determination of pp65-, p72- and p150-antigenemia and viremia in 7 (4 heart or heart-lung transplanted and 3 AIDS) immunosuppressed patients. These parameters were correlated with appearance of clinical symptoms and with their disappearance following antiviral treatment. Onset and progression of HCMV infection was associated to increasing levels of pp65-, p72- and p150-antigenemia and viremia, and a significant correlation was found between antigenemia and viremia in both PMNL and MNL. pp65-antigenemia showed absolute levels higher than p72- and p150-antigenemia both in PMNL and MNL, but PMNL showed figures consistently higher than MNL for all 3 viral proteins. levels of p150-antigenemia and viremia > 100 were associated to clinical symptoms in patients with peak of infection within 40 days after transplantation. In addition, number of HCMV-infected circulating giant cells (CGC) progressively increased in the presence of an organ syndrome. Antiviral treatment with either foscarnet or ganciclovir induced rapid disappearance of p150-positive PMNL and MNL as well as CGC, followed by disappearance of p72-positive leukocytes within a few days. pp65-positive cells were the last to disappear. Reported data suggest that viral replication may occur not only in MNL, but also in PMNL. Interaction between HCMV-infected circulating leukocytes and CGC may represent one of the major pathogenetic pathways for the development and dissemination of HCMV infection in immunocompromised patients.