Two patients with primary Epstein-Barr virus (EBV) infection followed by pancytopenia were studied. They showed increased numbers of DR-positive, activated T-cells and serological evidence of persistent EBV infection over a 12 and 18 week period. Bone marrow granulocyte-macrophage colony formation (CFU-GM) was investigated by limiting dilution assay (LDA) and methylcellulose assay. CFU-GM of bone marrow mononuclear cells (BMMNC) was markedly suppressed in both patients during the pancytopenic phase. Removal of bone marrow T-cells by E-rosetting resulted in a significant increase of CFU-GM to normal levels in BMMNC of both patients, while no significant increase was observed in the BMMNC of normal subjects. CFU-GM in BMMNC from Patient 1 in the recovery phase was normal when DR-positive T-cells were within normal levels, irrespective of the presence or absence of T-cells. These results suggest that pancytopenia due to infectious mononucleosis in these patients was due to bone marrow suppression by activated T-cells. In vitro studies with Con A activated T-cells and their culture medium showed that suppression of CFU-GM by T-cells was mediated by a lymphokine.