A patient with chronic myelogenous leukemia (CML) in chronic phase (CP) had been treated with a syngeneic bone marrow transplantation (BMT). Cytogenetic remission was confirmed 3 months later. One year after transplantation, hematological remission persisted while cytogenetic analysis revealed a recurrence of Philadelphia chromosome (Ph1). Five months later, we began treatment with human lymphoblastoid interferon (HLBI), a natural interferon (IFN)-alpha. Fourteen months after initiation of HLBI administration, cytogenetic analysis of the patient's bone marrow showed disappearance of Ph1 positive cells. One year after confirming cytogenetic remission, the absence of bcr-abl transcripts by polymerase chain reaction (PCR) assay indicated molecular remission. IFN therapy appears to be the first choice of treatment for cytogenetic relapse after syngeneic BMT. The efficacy of IFN appears to be due to an anti-malignancy effect, not to graft versus leukemia (GVL) effect.