Forty-eight adult leukemic recipients of HLA-identical sibling marrow were randomized to T cell depletion using anti-CD8 and anti-CD6 antibodies plus complement (n = 28) or prophylaxis with methotrexate (MTX) and cyclosporine (CsA) (n = 25). Patient characteristics were comparable in the two groups. The median observation time was 5 1/2 years. Transfusions, infections, and acute GVHD did not differ between the groups. Chronic GVHD occurred in 52% of patients receiving T cell-depleted marrow and 23% of those receiving MTX + CsA (P = 0.06). Overall probability of relapse was similar in both groups and actuarial leukemia-free survivals at 5 years were 39% and 35% in the two groups, respectively. Among patients with chronic myeloid leukemia (CML), leukemia-free survival at 5 years was 25% in patients receiving T cell-depleted marrow compared with 51% in those given MTX + CsA (P = 0.09). In patients with acute leukemia the probability of relapse was 24% in the group receiving T cell-depleted marrow compared with 73% in those treated with MTX + CsA (P = 0.06). Leukemia-free survival was 55% and 21% in the two groups, respectively (NS). CML patients tended to have a poorer prognosis and those with acute-leukemia better outcome with T cell depletion than with combined MTX + CsA. It is concluded that T cell depletion is unsuitable for patients with CML, but may be considered in patients with acute leukemia.