MUTATIONS in the KIT transmembrane protein-tyrosine kinase receptor¹ affect erythropoiesis, resulting in fewer committed late progenitors (colony-forming unit erythroid, CFU-E) in the fetal liver². As the survival and proliferation of CFU-Es depend absolutely on erythropoietin (EPO)³, these results suggest that CFU-Es cannot proliferate or mature further unless both the KIT and EPO receptor⁴ signalling pathways are functional. How KIT affects proliferation or differentiation of CFU-Es is not clear. Here we show that the KIT ligand SCF (for stem-cell factor) can replace EPO in supporting the growth and survival of HCD57 cells, an EPO-dependent erythroid-progenitor cell line expressing high levels of KIT⁵. SCF supports the proliferation of 32D cells⁶ that express KIT only if they also express the EPO receptor. In HCD57 cells, SCF rapidly induces tyrosine phosphorylation of the EPO receptor, and KIT physically associates with the extended box 2 region⁷ in the cytoplasmic domain of the EPO receptor. Our results indi-cate that KIT may activate the EPO receptor by tyrosine phosphorylation to induce further proliferation and maturation of CFU-Es.