Although the combination of cyclosporin A (CYA) and methotrexate has been reported to reduce the incidence of acute GVHD in patients undergoing allogeneic BMT for leukaemia, it has been associated with a higher risk of leukaemic relapse. Since 1987 we have used the combination of CYA and methotrexate for GVHD prophylaxis in 24 patients undergoing allogeneic BMT for leukaemia or myelodysplasia. Over the first 50 days post-transplantation, CYA dosage was adjusted to keep within a therapeutic range of 95-205 ng/ml. This resulted in a 60% reduction in CYA dosage by day 50 post-transplant compared to the original Seattle protocol. Despite the low dosage of CYA administered, the incidence of acute GVHD was only 25% with no patient having greater than grade I GVHD. There have been no leukaemic relapses in low risk patients. The results indicate that decreasing CYA dosage does not increase the incidence of GVHD but may reduce the risk of leukaemic relapse following allogeneic BMT.