One hundred seventy-nine patients with acute nonlymphoblastic leukemia in first remission (n = 75), chronic myelocytic leukemia in chronic or accelerated phase (n = 48) or leukemia in advanced stage (n = 56) were given HLA-identical marrow grafts and randomized to receive methotrexate or cyclosporine for prevention of graft-v-host disease (GVHD). The current report updates the three prospective trials with follow-ups ranging from 3.2 to 6.2 years after marrow grafting. Results were analyzed separately for each individual study and for all three studies combined. Overall, 40% of patients given cyclosporine and 55% of those given methotrexate developed acute GVHD (P = .13); the incidence of chronic GVHD was 42% and 48%, respectively (P = .67). Twenty-two percent of cyclosporine-treated patients and 30% of methotrexate-treated patients developed interstitial pneumonia of any etiology (P = .25), and the figures for cytomegalovirus pneumonia were 18% and 20%, respectively (P = .41). The overall incidence of leukemic relapse was 31% in cyclosporine-treated patients and 36% in methotrexate-treated patients (P = .75). The probabilities of survival for cyclosporine-v methotrexate-treated patients were comparable for all three study groups: 52% v 48% in patients with acute nonlymphoblastic leukemia (P = .42), 55% v 60% for those with chronic myelocytic leukemia (P = .61), 12% and 12% for those with advanced leukemia (P = .93), and 39% v 38% overall (P = .72). We conclude that cyclosporine and methotrexate are comparable regarding the likelihood of acute/chronic GVHD, interstitial pneumonia, leukemic relapse, and long-term survival.