Erythropoietin (Epo) induces a dose-dependent increase in intracellular free calcium concentration ([Cai]) in single human BFU-E derived erythroblasts, which is specific for stage of differentiation and mediated through a voltage-independent ion channel permeable to calcium. This minireview examines the regulation of calcium channels by Epo during normal erythroid differentiation, as a model to delineate the immediate signaling events which follow interaction of Epo with its receptor.