Blood pressure measured immediately after a brief period of upright leg exercise was considerably lower than the resting standing blood pressure in 38 hypertensive patients treated with guanethidine or debrisoquin. The hemodynamic mechanism of this hypotension after exercise was studied in 6 hypertensive patients given guanethidine intravenously and in 16 patients treated with effective oral doses of guanethidine or debrisoquin. Intravenous and oral drug treatment blocked the reflex forearm vasoconstriction that normally occurs during leg exercise. Although supine exercise was associated with a modest fall in arterial pressure from hypertensive levels, the most dramatic effects of the blocking agents on the response to exercise were observed when patients were in the upright position. Blood pressure rose from normal to above normal levels during exercise and fell promptly to below resting levels when leg movement was stopped. Upright leg exercise in the treated patients was accompanied by a large increase in cardiac output and a sharp fall in leg volume. Immediately after exercise, cardiac output fell moderately and leg volume rapidly increased. These studies suggest that alterations in the hemodynamic response to exercise induced by sympathetic blocking agents are due both to inhibition of reflex arteriolar constriction and to large passive shifts in blood volume that occur in the upright position as a result of blockade of venous reflex adjustments. Hypotensive symptoms related to exertion probably result from the combined effects of gravitational pooling after exercise and a persistently low peripheral vascular resistance. These symptoms can promptly be corrected by reinstitution of leg exercise. It is suggested (1) that immediately after upright leg exercise the blood pressure is more sensitive to mild degrees of adrenergic blockade than when patients are in the resting standing position and (2) that the postexercise blood pressure may serve as a more reliable guide to adjustment of the dose of sympathetic blocking agents in patients with hypertension.