Immunologic evidence is presented that the interaction of Renal Erythropoietic Factor (REF) and a serum substrate results in the production in vitro of erythropoietin. Antibody capable of neutralizing erythropoietin (ESF) does not combine with either the REF or the serum substrate. Immune serum against the crude REF extract has been produced. This immune serum does not prevent the in vitro action or in vivo production of REF. This failure, however, may result from the diversity of antibodies produced.