Nine normotensive volunteers underwent six days of sodium-depletion followed by six days of sodium-repletion. On days six and twelve, the angiotensin II inhibitor, sar1-ala8-angiotensin II (saralasin), was infused i.v. and the blood pressure monitored with the subjects first in supine and then in upright position. The degree of induced sodium-depletion was varied over a considerable range in order to determine the level of sodium balance which is critical for maintaining blood pressure in the absence of the pressor action of angiotensin II. Five subjects had a cumulative sodium loss of more than 200 mEq, mainly because of more vigorous diuretic treatment; upon infusion of saralasin, four exhibited marked hypotension in the erect position. The fifth became deeply hypotensive while still supine and was unable to stand up. Hypotension occurred in spite of clinical evidence of catecholamine oversecretion. In the four patients who had urinary sodium losses of less than 200 mEq, infusion of the inhibitor did not reduce their blood pressure. Following sodium-repletion, none of the nine subjects exhibited a blood pressure response to the inhibitor. These results suggest that angiotensin II plays an active role in sustaining normal blood pressure only under conditions of considerable sodium-depletion.