Five patients with idiopathic orthostatic hypotension who had physiologic and biochemical evidence of severe autonomic dysfunction were included in the study. They all exhibited markedly reduced plasma catecholamines and plasma renin activity in both recumbent and upright positions and had marked hypersensitivity to the pressor effects of infused norepinephrine. Treatment with propanolol administered intravenously (1-5 mg) produced increases in supine and upright blood pressure in 4 of the 5 individuals with rises ranging from 11/6 to 22/11 mmHg. Chronic oral administration of propranolol (40-160 mg/day) also elevated the blood pressures of these individuals with increases in the order of 20-35/15-25 mmg being observed. In 1 patient, marked hypertension was induced by propranolol and the drug had to be withdrawn. It otherwise was well tolerated and no important side effects were observed. Treatment has been continued in 3 individuals for 6-13 months with persistence of the pressor effect, although there appears to have been some decrease in the degree of response with time. Hemodynamic measurements in 1 of the patients demonstrated an increase in total peripheral resistance and essentially no change in cardiac output following propranolol therapy. The studies suggest that propranolol is a useful drug in selected patients with severe idiopathic orthostatic hypotension.