Plasma concentrations of IR endothelin are elevated in patients with chronic renal failure. But its exact causes have not been clarified. Hypertension may be one of the most important factors associated with elevated plasma IR endothelin concentrations, although it still remains to be determined whether hypertension is a result or a cause of the elevated plasma IR endothelin concentrations in patients with chronic renal failure. Elevation of plasma IR endothelin concentrations was found in hemodialysis patients with rHuEPO-induced blood pressure elevation. Endothelin may be one of the causes in rHuEPO-induced hypertension in some hemodialysis patients. Endothelin receptors have been cloned, and several endothelin antagonists have been reported. The studies using clinically useful endothelin antagonists will further clarify the pathophysiology of endothelin in patients with chronic renal failure.