Injection of 10(6) immortalized, but non-leukemic, granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent FDC-P1 cells into GM-CSF transgenic hybrid mice with elevated GM-CSF levels led to death within three months with elevated blast cell numbers in the blood, massive organ infiltration by blast cells, and associated anemia and thrombocytopenia. No disease developed within this period in littermate mice injected with 10(6) FDC-P1 cells. All moribund transgenic recipients contained transformed FDC-P1 cells able to produce rapidly-growing transplanted leukemias in syngeneic normal DBA/2 recipients. The leukemias appeared to arise in the primary recipients by independent transformation events. The transformed cells from different mice differed in their in vitro growth characteristics, their ability to produce GM-CSF or multipotential CSF, and in the nature of the transplanted tumors derived from the primary cells. While all primary recipients at death contained fully transformed leukemic cells, the bulk of the large population of FDC-P1 cells appeared either to be untransformed or to have altered characteristics not yet representing full transformation. If the FDC-P1 engrafted model has some validity for myelodysplasia, the results suggest that sustained CSF administration to myelodysplastic patients possessing abnormal, potentially preleukemic, granulocyte-macrophage populations may increase the risk of death either from accumulated pretransformed or from fully transformed leukemic cells.