The principal function of erythrocytes is the transport of oxygen. Erythropoiesis proceeds at a rate consistent with the demand for oxygen-carrying capacity, and the major regulator of erythrocyte production is erythropoietin. Erythropoietin is produced primarily by the kidney under control of a tissue oxygenation sensor. The recently developed erythropoietin radioimmunoassay should provide a clinically useful tool. Erythrocytosis is a pathologic state characterized by an elevated erythrocyte mass, which may result from increased proliferation of erythroid progenitors due to an intrinsic cellular defect or in response to extrinsic signals. Secondary erythrocytosis results from either physiologically appropriate compensation for inadequate tissue oxygenation or from inappropriate stimulation of erythropoiesis. Erythrocytosis increases oxygen-carrying capacity of the blood, but at high hematocrit levels increased blood viscosity may result in decreased tissue oxygen delivery. Polycythemia vera is a hematopoietic stem cell disease of clonal origin. Initial results from the Polycythemia Rubra Study Group suggest that therapy with chlorambucil is associated with an unacceptably high risk for development of acute leukemia, and 32P is preferred for situations in which phlebotomy alone is insufficient.