Refractory acute lymphoblastic leukemia (ALL) is often incurable, and relapse rates following allogeneic bone marrow transplantation (BMT) remain high. We have reported that patients who develop increased numbers of γδ+ T cells soon after BMT are significantly less likely to relapse. We now show in seven donor/recipient pairs that donor-derived Vδ1+ CD4− CD8− γδ+ T cells are activated and proliferate in response to recipient primary ALL blasts. In addition, these cells have been shown to bind and lyse the recipient ALL blasts. Separately, γδ+ T cells proliferate poorly or not at all in mixed lymphocyte culture against HLA-mismatched unrelated stimulator cells. These observations suggest that allogeneic γδ+ T cells could be an effective immunotherapeutic strategy against refractory disease without the risk of graft-versus-host disease. Bone Marrow Transplantation (2001) 27, 601–606.