Human herpesvirus 6 (HHV-6) has been reported to be involved in bone marrow failure after bone marrow transplantation (BMT). To elucidate the role of HHV-6 in the marrow failure, we examined the comparative effect of two variants of HHV-6 (HHV-6A and HHV-6B) and human herpesvirus 7 (HHV-7) on in vitro colony formation of hematopoietic progenitor cells in methylcellulose semi-solid media. Progenitor cells prepared from cord blood mononuclear cells (CBMNCs) were infected with one of these viruses at various multiplicity of infection (MOI), and were subjected to methylcellulose colony assay. Formation of both granulocyte/macrophage (CFU-GM) and erythroid (BFU-E) colonies was MOI-dependently suppressed after infection with the Z29 strain of HHV-6B. Although HHV-6A suppressed the formation of BFU-E colonies as efficiently as HHV-6B, the former did not exhibit significant suppressive effect on the formation of CFU-GM colonies at an MOI 1. HHV-7 had no effect on hematopoietic colony formation at all. Based on frequent positivity of viral DNA in single colonies obtained from HHV-6-infected progenitor cells by polymerase chain reaction and in situ hybridization, direct effects of HHV-6 on the hematopoietic progenitor cells are suggested as the cause of the suppression rather than indirect effects via accessory cells of the bone marrow.