Allogeneic hematopoietic cell transplantation can be curative in patients with leukemia and lymphoma. However, progressive growth of malignant cells, relapse after transplantation, and graft-versus-host disease (GVHD) remain important problems. The goal of the current murine study was to select a freshly isolated donor T-cell subset for infusion that separates antilymphoma activity from GVHD, and to determine whether the selected subset could effectively prevent or treat progressive growth of a naturally occurring B-cell lymphoma (BCL₁) without GVHD after recipients were given T cell–depleted bone marrow transplantations from major histocompatibility complex–mismatched donors. Lethal GVHD was observed when total T cells, naive CD4⁺ T cells, or naive CD8⁺ T cells were used. Memory CD4⁺CD44^hi and CD8⁺CD44^hi T cells containing both central and effector memory cells did not induce lethal GVHD, but only memory CD8⁺ T cells had potent antilymphoma activity and promoted complete chimerism. Infusion of CD8⁺ memory T cells after transplantation was able to eradicate the BCL₁ lymphoma even after progressive growth without inducing severe GVHD. In conclusion, the memory CD8⁺ T-cell subset separated graft antilymphoma activity from GVHD more effectively than naive T cells, memory CD4⁺ T cells, or memory total T cells.