The objective of this investigation was to characterize the mechanism of peripheral vasoconstriction observed in heart failure and to determine whether it can be attributed to the augmented sympathetic nervous activity, characteristic of this state. The response of the resistance bed in the forearm after release of inflow occlusion (reactive hyperemia), to hand exercise, and to local heating and the response of the calf resistance vessels to arterial occlusion and intra-arterial sodium nitrite and phentolamine were studied in 23 patients with congestive heart failure and 21 normal subjects. In the normal subjects, reactive hyperemia blood flow after varying periods of arterial occlusion greatly exceeded the values observed in patients with heart failure. Local anesthetic blockade and intra-arterial phentolamine did not significantly alter the reactive hyperemia response in heart failure patients, militating against the possibility that increased sympathetic vasoconstrictor activity is responsible for the reduction of this response. Following compensation, the reactive hyperemia response returned toward normal. The striking elevations of the forearm blood flow observed after hand exercise and heating of the forearm in normal subjects were also markedly attenuated in patients with heart failure. Following intra-arterial phentolamine and/or sodium nitrite, peak calf blood flow was still significantly reduced in heart failure. These observations indicate that (1) heart failure is characterized by a striking reduction in the response to a variety of endogenous and exogenous vasodilator stimuli; (2) circulating catecholamines and sympathetic vasoconstrictor activity are not solely responsible for the elevation of peripheral vascular resistance and the reduced response to vasodilator stimuli in heart failure; and (3) heart failure may increase systemic vascular resistance directly by altering the mechanical properties and reducing the dilating ability of the resistance vessels.