The feasibility and toxicity of allogeneic stem cell transplantation after nonmyeloablative conditioning including thiotepa, fludarabine, and cyclophosphamide have been investigated in 6 patients with breast cancer and 7 patients with renal cell cancer. The program included the use of escalating doses of donor lymphocyte infusions (DLI) and/or interferon alpha (IFNalpha) for patients showing no tumor response and no graft-versus-host disease (GVHD). Patients were at high risk of transplant-related mortality (TRM) because of age, advanced stage, and previous treatments. We observed a partial remission in 4 renal cancer and in 2 breast cancer patients (one at the molecular level in the bone marrow), occurring after cyclosporine withdrawal or after DLI and/or IFNalpha. All the responses were accompanied by the occurrence of acute GVHD. We conclude that reduced-intensity allogeneic stem cell transplantation is a feasible procedure in renal and breast cancer, and that the exploitation of graft-versus-tumor effect after DLI is a promising finding.