A 21-year-old woman with chronic myelogenous leukemia (CML) relapsed into lymphoblastic crisis with new chromosomal translocations, 4 months following mismatched unrelated allogeneic bone marrow transplantation (BMT). Adoptive cell-mediated immunotherapy with mismatched unrelated donor lymphocytes followed by 3 days of in vivo interleukin-2 (IL-2) resulted in complete remission including disappearance of the Philadelphia chromosome as determined by cytogenetic analysis and the bcr/abl translocation detected by PCR. Lymphoblastic crisis following mismatched, unrelated BMT is relatively rare. Moreover lymphoblastic malignancies usually respond less favorably to cell-mediated immunotherapy. This case is the first reported CML lymphoblastic crisis following mismatched unrelated BMT that responded to cell-mediated immunotherapy and IL-2. Some possible mechanisms and new therapeutic directions are discussed.