In twelve separate studies employing hypertransfused mice, attempts were made to demonstrate the generation of erythropoietin from normal serum incubated with the "Renal Erythropoietic Factor." Despite the use in some studies of preparations found effective in another laboratory, these attempts were all unsuccessful. It is concluded that the hypothesis that erythropoietin is produced by the enzymatic activation of an inactive circulating protein needs much further study before it can be accepted.