Pretransplant herpes virus serology and acute graft-versus-host disease (GVHD) were studied in 379 leukaemic bone marrow transplant (BMT) recipients and their HLA-identical sibling donors. In logistic multivariate regression analysis pretransplant seropositivity to three or more different herpes viruses among the recipients was the only significant factor associated with grade II-IV acute GVHD (p = 0.03). If this factor was excluded, older donor age (p less than 0.001), absence of T cell depletion (p less than 0.001), pharmacological immunosuppression by monotherapy of methotrexate or cyclosporin versus a combination therapy of both (p = 0.002), and seropositivity to three or more herpes viruses among the donors (p = 0.03) prior to BMT, were also significantly associated with acute GVHD. The data indicate that latent herpes viruses in the host may act as minor histocompatibility antigens or by other means to trigger acute GVHD.