Abnormalities of cortisol production or metabolism are involved in the genesis of hypertension in Cushing's syndrome, apparent mineralocorticoid excess and liquorice abuse and possibly in chronic renal failure and essential hypertension. We have studied the physiological mechanisms by which cortisol raises blood pressure in short term studies of cortisol administration in normal men. Cortisol induced hypertension cannot be explained by increases in vasopressor or decreases in vasodepressor hormone concentrations, or by any increase in sympathetic nervous activity. The hypertension is accompanied by substantial sodium retention but a significant component of the blood pressure rise is sodium independent. The hypertension is characterized by an increase in cardiac output but a rise in output is not essential for the rise in blood pressure. Our working hypothesis is that cortisol induced hypertension is a consequence of increases in renal vascular resistance.