Proliferation in vitro of the murine hemopoietic cell line FDC-P1 is dependent on stimulation by granulocyte-macrophage colony stimulating factor or multipotential colony stimulating factor. Although immortalized, the cells are not tumorigenic on subcutaneous inoculation. Intravenous injection of FDC-P1 cells into syngeneic DBA/2 mice was followed by the development of transplantable leukemias in 15% of nonirradiated animals and in virtually all animals that had received 100-350 rad whole-body irradiation prior to injection. Karyotypic analysis showed that the leukemias originated from FDC-P1 cells, and primary tumor cells from different animals displayed a wide spectrum of altered growth patterns when cultured in agar. In most cases, colony formation by leukemic cells in vitro exhibited autonomy with respect to stimulation by exogenous colony stimulating factors. These observations indicate that leukemic transformation of FDC-P1 cells is enhanced by irradiation of recipient mice and document a useful model for analyzing the mechanisms by which irradiation induces leukemia.