Patients with severe hematologic disorders may have elevated erythropoietin titers in plasma or urine at higher hemoglobin concentrations than those associated with elevated titers in experimental animals or patients anemic as a result of simple blood loss. Patients with "primary" hematologic disease may have a measurable titer of erythropoietin in the plasma and urine at hemoglobin concentrations up to 8 Gm./100 ml., but patients with iron-deficiency anemia show elevated titers in the urine only with hemoglobin concentrations at or below 4 Gm./100 ml. and in the plasma below 5 Gm./100 ml. The abruptness with which the titer rises and the severity of the anemia required before measurable titers appear are similar in man and in rabbits, sheep and dogs. The fact that no measurable erythropoietin titer can be demonstrated when the hemoglobin concentration is well below that required for intense stimulation of erythropoiesis and the abruptness of the rise at hemoglobin concentration of 4 Gm./100 ml. or less suggest that erythropoietin may not be an important factor in the control of erythropoiesis except in extreme circumstances. On the other hand, these facts may be explained more simply by the insensitivity of the assay methods used.