Allogeneic bone marrow transplantation is the only curative treatment for patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML); however, recurrence of disease remains a major cause of treatment failure. A 26-year-old man with chronic myeloid leukemia who had a cytogenetic relapse 49 months after his first syngeneic bone marrow transplant (BMT) and hematologic relapse 23 months thereafter progressed to blast crisis despite treatment with IFN-alpha for 15 months. He underwent a second transplantation in early second blast crisis, 92 months after the first BMT with PBPC from his previous donor. Successful hematological reconstitution occurred. On day 50 after the second transplantation the patient developed a generalized rash, hepatomegaly, and cholestatic signs. Skin and liver biopsy revealed changes compatible with acute graft-versus-host disease (GVHD). Treatment with cyclosporin A (CSA) and prednisone was started, and the GVHD resolved. Fifteen months after PBPC transplantation he had a molecular relapse. Despite discontinuation of CSA, the patient progressed into blast crisis 7 months later. The occurrence of GVHD and disappearance of the BCR-ABL-positive clone suggest that a graft-versus-leukemia (GVL) effect may have been operative for 15 months in a patient given a second syngeneic BMT in blast crisis.