Experiments were done to study the effects of acute changes in plasma sodium concentration [Na] on vasoconstrictor responses to norepinephrine and to reflex sympathetic stimulation in man. [Na] in the venous return from the forearm of each of 21 normal subjects was reduced (to an average of 118 mEq/liter), increased (147 mEq/liter), and maintained within the normal range (140 mEq/liter) by means of infusions into the brachial artery of three solutions containing different [Na]. Mannitol or sucrose and disodium sulfate were substituted for sodium chloride to produce the desired changes in [Na] without changing blood osmolarity. Blood flow to the forearm (plethysmograph) increased during infusion of the three solutions, but the increase in flow was not related to [Na]. Vasoconstrictor responses to injections of norepinephrine and angiotensin into the brachial artery were reduced at low [Na] and augmented at high [Na]. Reflex vasoconstriction, activated by lower body negative pressure, was similarly affected by changes in [Na]. In the isolated, perfused gracilis muscle of dog vasoconstrictor responses to norepinephrine and to nerve stimulation were attenuated, and the extraction of norepinephrine by this muscle was smaller when plasma [Na] was reduced.