In tumor cells from virtually all patients with chronic myelogenous leukemia, the Philadelphia chromosome, a fusion of chromosomes 9 and 22, directs the synthesis of the P210^bcr/abl protein. The protein-tyrosine kinase activity and hybrid structure of P210^bcr/abl are similar to the oncogene product of the Abelson murine leukemia virus, P160^gag/v-abl, which induces acute lymphomas. To determine whether P210^bcr/abl can induce chronic myelogenous leukemia, murine bone marrow was infected with a retrovirus encoding P210^bcr/abl and transplanted into irradiated syngeneic recipients. Transplant recipients developed several hematologic malignancies; prominent among them was a myeloproliferative syndrome closely resembling the chronic phase of human chronic myelogenous leukemia. Tumor tissue from diseased mice harbored the provirus encoding P210^bcr/abl. These results demonstrate that P210^bcr/abl expression can induce chronic myelogenous leukemia. Retrovirus-mediated expression of the protein provides a murine model system for further analysis of the disease.