Stem cell factor and its receptorc-kitconstitute an important signal transduction system implicated in survival, proliferation, and differentiation of stem cells in hematopoiesis, gametogenesis, and melanogenesis. In the present study we used both immunocytochemical methods and Western analysis to demonstrate the presence of this cytokine/receptor system in both embryonic and adult rat liver. Stem cell factor was present in the ductular cells around the portal vein during the late embryonic stage of the liver. In the adult liver both bile ducts and bile ductules were positive for stem cell factor andc-kit.When the activation of the liver stem cell compartment was induced by combining administration of acetylaminofluorene and partial hepatectomy, both stem cell factor andc-kitwere expressed in the infiltrating oval cell population, but absent in the newly formed basophilic hepatocytes. Activation of oval cell proliferation following administration ofD-galactosamine also produced a similar but less prominent increase in the level of the stem cell factor. Our data suggest that the stem cell factor/c-kitsignal transduction system is involved in the development of bile ducts and that it may also be an important member of the growth factor/receptor systems associated with the biology of liver stem cells.