MEGAKARYOCYTOPOIESIS is the cellular developmental process that leads to platelet production. At least two humoral growth factors mag be necessary for megakaryocyte proliferation and maturation. One is a megakaryocyte-colony stimulating factor (MK-CSF) which induces the proliferation and differentiation of megakaryocyte progenitors(1,2), and the second, thrombopoietin, is a megakaryocyte maturation factor(3). Neither of these factors has been fully characterized. The proto-oncogene c-mpl, an orphan member of the haematopoietin receptor family(4-6), is specifically involved in megakaryocyte regulation(7). Here we present evidence that the c-mpl-encoded receptor binds a ligand (c-Mpl ligand) which is a humoral factor implicated in platelet homeostasis. Our results suggest that c-Mpl ligand, thrombopoietin and MK-CSF might be the same molecule.