A chimeric BCR/ABL oncogene encoding the p190 protein has been introduced into the mouse germline using microinjection of one-cell fertilized eggs. Founder and progeny transgenic animals, when becoming ill, were found to develop lymphoblastic leukemia/lymphoma which was transplantable to compatible recipients. Lymphoblasts were arrested at the pre-B stage of development. Expression of BCR/ABL was not detected in peripheral blood during the early stages of leukemia but became evident as the disease progressed. However, the transgene was expressed early in development in bone marrow and was also transcribed in nonhematopoietic tissues although this did not result in tumorigenesis. These results strongly suggest that the oncogenicity of BCR/ABL is limited to hematopoietic cells, including pre-B cells or their progenitors.