Human cytomegalovirus, HCMV, infects most of the population by adulthood; The primary infection is often accompanied by transient neutropenia and thrombocytopenia, and is followed by a period asymtomatic viral latency. In the setting of bone marrow transplantation, however, the immunosuppressed state of the recipient enables HCMV to re-activate or to infect the individual and cause serious sequelae. These range from hepatitis and gastrointestinal disease to interstitial pneumonia and hematologic abnormalities, which are more common in the allograft. Little is currently known about the mechanisms by which HCMV causes these hematologic abnormalities. In this review, we discuss experimental models which are helping investigators understand the immunology and pathology of CMV infection. We also summarize the vivo studies of the effects of HCMV on human hematopoiesis. Several possible mechanisms that could explain the deleterious effect of HCMV on human hematopoietic function include: 1) alteration of accessory cell function by inducing the production of inhibitory cytokines; 2) perturbation of stromal cell function resulting in a decreased production of hematopoietic factors or by altering cell surface adhesion molecule expression; 3) by direct infection of the hematopoietic stem or progenitor cells. It is likely that the pathogenesis of this syndrome is multifactorial therefore requiring a broad therapeutic approach. This would include the use of the antiviral agents, hematopoietic growth factors and donor derived HCMV specific cytolytic cells.