We studied 2254 persons receiving HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) in first remission, or chronic myelogenous leukemia (CML) in first chronic phase to determine whether graft-versus-leukemia (GvL) reactions are important in preventing leukemia recurrence after bone marrow transplantation. Four groups were investigated; recipients of non-T-cell depleted allografts without graft-versus-host disease (GvHD), recipients of non-T-cell depleted allografts with GvHD, recipients of T-cell depleted allografts, and recipients of genetically identical twin transplants compared with recipients of non-T-cell depleted allografts without GvHD, Decreased relapse was observed in recipients of non-T-cell depleted allografts with acute (relative risk 0.68, P = 0.03), chronic (relative risk, 0.43, P = 0.01), and both acute and chronic GvHD (relative risk 0.33, P = 0.0001). These data support an anti-leukemia effect of GvHD. AML patients receiving identical twin transplants had an increased probability of relapse (relative risk 2.58, P = 0.008) compared to allograft recipients without GvHD supporting an anti-leukemia effect of allografts independent of GvHD. CML patients receiving T-cell depleted transplants without GvHD had a higher probability of relapse (relative risk 6.91, P = 0.0001) than recipients of non-T-cell depleted allografts without GvHD. These data support an antileukemia effect independent of GvHD altered by T-cell depletion. These results indicate that much of the anti-leukemia effect of bone marrow transplants is related to immune factors rather than high-dose chemotherapy and/or radiation.