51 patients received allogeneic marrow from histocompatible and MLR non-reactive siblings. Post-transplantation methotrexate was associated with acute refractory graft-versus-host disease (GVHD) in 10/23 (43%) and caused death in 6. When cyclosporin was substituted for the methotrexate fulminating GVHD occurred in 2/28 (28%): both responded to methylprednisolone. When both donor and recipient were pretreated with cyclosporin GVHD of only mild degree developed in 6/20 (30%): 2 responded rapidly to methylprednisolone and in the remaining 4 mild cutaneous lesions persisted. The latter regimen was associated with no donor morbidity and approximately 50% of the recipients had easily reversible renal dysfunction. Thus, cyclosporin A appears to marginally reduce the incidence of acute GVHD and to facilitate response when additional methylprednisolone is required: additional pretreatment of the donor appears to reduce the severity of the acute syndrome. In none of these regimens was a beneficial effect observed on de novo GVHD.