Erythropoietin titers were measured in anemic nephric and anephric patients undergoing chronic hemodialysis by utilizing a plasma concentration technique. In eight out of 11 anephric patients studied, decreased but detectable levels of erythropoietin were found, suggesting that extrarenal erythropoietin plays a role in the regulation of red cell production in anephric patients. In 14 nephric uremic patients, erythropoietin production was found to be more variable, with one group of eight patients having erythropoietin levels in the range for normal nonanemic individuals (3.9 to 15 mU/ml), and a second group of six patients with erythropoietin higher than normal (greater than 15 mU/ml). Both groups were found to be equally anemic, indicating that in the second group the bone marrow is less responsive to erythropoietin. The severity of secondary hyperparathyroidism was found to be higher in this second group, suggesting a role of PTH in the bone marrow unresponsiveness. A good correlation between biological and immunological erythropoietin activities was found in the plasma from normal subjects and uremic nephric and anephric patients.