Hematopoietic stem cell transplantation provides effective therapy for patients with a variety of hematologic malignancies, but this continues to be a very intensive and potentially dangerous treatment approach. With recent improvements in supportive care, the most common causes of treatment failure are disease relapse and infectious complications associated with immune deficiency following transplant. To address these 2 issues, my laboratory research is focused on the characterization of immune reconstitution following allogeneic hematopoietic stem cell transplantation. It is now well established that reconstitution of donor hematopoiesis not only replaces the recipients own immune system but also results in the development of immunity against patient tumor cells. This development of anti-tumor immunity is very effective and plays an important role in the prevention of relapse following stem cell transplantation. Both laboratory projects and clinical trials are attempting to define the immunologic mechanisms as well as the target antigens of this response. With better understanding of the mechanisms and target specificity of the graft-versus-leukemia (GVL) response, it will be possible to distinguish GVL from graft-versus-host disease (GVHD) and to develop new methods for selectively enhancing GVL.