OBJECTIVES: Erythropoietin is a hormone of considerable biologic and pathophysiologic importance. It provides a crucial link in the feedback system which adjusts the rate of red cell production to the need for oxygen in the tissues and it acts by transforming committed but still undifferentiated stem cells to erythroblasts. The objective of the proposed research is to elucidate these functions by studies of its mode and site of production, its metabolism and its interaction with bone marrow cells. METHODS OF PROCEDURE: The general method of procedure will be to correlate erythropoietin production with measurements of oxygen transport parameters such as arterial pO2, 2,3 DPG, arterial pH and p50, erythrokinetic parameters, such as bone marrow examination, iron turnover and iron utilization and stem cell parameters such as numeration of BFU-E and CFU-E on in vitro cultures. Erythropoietin production will be evaluated by regular consumption of erythropoietin, by radioimmunoassay being developed and by CFU-E response in bone marrow cultures. Patients with polycythemia and patients with anemia, especially aplastic anemia, hemolytic anemia, renal anemia, and anemia of chronic disease will be studied. These studies will be correlated with studies of experimental animals in whom similar disease processes have been induced.