Hemopoietic growth factors have been implicated in the pathogenesis of some myeloid leukemias when the cells acquire the autocrine capacity to produce a relevant growth factor. We report transformation of the immortalized cell line FDC-P1 by overexpression of murine c-fms, the receptor for macrophage colony-stimulating factor (M-CSF). Three types of cell lines were obtained following expression of c-fms in FDC-P1 cells. The first type of cell line (FD-c-fms) was dependent on stimulation by M-CSF to induce cell proliferation and also underwent limited monocytic/macrophage differentiation in response to M-CSF. The second type of cell line (FD-c-fmsi) was able to proliferate in serum-containing cultures without stimulation by exogenous hemopoietic regulators. Stimulation of the FD-c-fmsi cell lines with M-CSF suppressed proliferation compared to cultures of unstimulated cells and induced monocytic/macrophage differentiation. The third type of cell line (FD-c-fms) was autonomous, failed to differentiate in response to M-CSF and secreted M-CSF into the culture medium, suggesting an autocrine mechanism of transformation. All three types of cell lines demonstrated varying degrees of suppression of cell proliferation when stimulated by the combination of M-CSF and GM-CSF. The data indicate that transformation of c-fms expressing cells results in a variety of phenotypes with dissociation of M-CSF induced proliferation and differentiation in different cell lines.