Stem cell factor (SCF), the ligand for the c-kit protooncogene product, was able to stimulate blast cell and granulocytic colony formation by precursors from normal murine bone marrow. The blast cell colonies contained a high content of progenitor cells able to form macrophage and/or granulocyte colonies. Clone transfer studies, the secondary culture of colony cells, and the culture of populations freed of accessory cells all indicated a direct proliferative action of SCF. SCF receptors were present in high numbers on blast cells and in lower numbers on immature granulocytic, monocytic, and eosinophilic cells. Combination of SCF with granulocyte, granulocyte-macrophage, or multipotential colony-stimulating factors, but not macrophage colony-stimulating factor, resulted in enhancement of colony size. Granulocyte colony-stimulating factor enhanced cell proliferation initiated by SCF, but not vice-versa, and resulted in a 10-fold increase in colony cell numbers and a 7-fold increase in progenitor cells in blast colonies. No evidence was obtained that SCF, alone or in combination with granulocyte colony-stimulating factor, could stimulate self-generation by blast colony-forming cells.