The human multilineage hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) induces multipotent, erythroid, and eosinophil colony formation from highly enriched normal bone marrow cells. We have examined the effects of GM-CSF combined with granulocyte-CSF (G-CSF) or macrophage-CSF (M-CSF) on the monolineage granulocytic, eosinophilic, and macrophage progenitor cells (CFU-G, CFU-Eo, and CFU-M) in accessory cell depleted marrow fractions. GM-CSF effects were assessed in direct comparison with those of interleukin-3 (IL-3) plus G-CSF or M-CSF. GM-CSF strongly synergized with G-CSF in the formation of granulocytic colonies with respect to number and size and enhanced the in vitro survival of CFU-G. More immature cells were present in colonies induced by the mixture of GM-CSF and G-CSF than by G-CSF alone. GM-CSF also synergized with M-CSF in the formation of macrophage colonies (number and size). The addition of G-CSF and M-CSF did not influence eosinophil colony formation induced by GM-CSF or IL-3. Experiments directly comparing GM-CSF and IL-3 revealed that the effects of GM-CSF on G and M colony-forming cells were significantly greater than those of IL-3. The potent positive effects between GM-CSF and G-CSF as well as between GM-CSF and M-CSF provide a powerful mechanism of amplification of granulopoiesis and monocytopoiesis.