The ability of T cells that accompany or develop from transplanted allogeneic marrow to eradicate leukemia has been repeatedly demonstrated in animal models. Whether a similar graft-versus-leukemia effect exists in humans who have received transplants for acute lymphoblastic leukemia can be addressed by five different clinical observations: comparisons of autologous versus allogeneic transplantation, comparisons of syngeneic versus allogeneic transplantation, examination of relapse rates in allogeneic recipients who do or do not develop GVHD, the impact of T-cell depletion on relapse rates, and the results of donor lymphocyte infusions to treat posttransplant relapse. The bulk of available evidence supports the view that a potent GVL effect exists in patients treated for ALL. These results provide a strong rationale for efforts to develop techniques to further capitalize on the GVL effect.