Abstract-Previous work has shown sensitization of carotid chemoreceptor (CC) responsiveness during exercise as well as in chronic heart failure (CHF). Accordingly, we hypothesized that the CCs contribute to the sympathetic restraint of skeletal muscle blood flow during exercise and CHF. We examined the effect of transient CC inhibition on total (Con T ) and hindlimb (Con L ) conductance, and blood pressure at rest and during exercise (2.5 miles per hour, 5% grade) in chronically instrumented dogs. Via a carotid arterial catheter, CCs were inhibited using dopamine (5 to 10 g/kg) or hyperoxic lactated Ringer's solution. Although vasodilation did not occur with CC inhibition in resting healthy dogs, CC inhibition during exercise caused an immediate vasodilatory response (increase in Con T and Con L and decrease in blood pressure). When comparing the peak Con L response from CC inhibition versus ␣-adrenergic blockade (phentolamine), we found that the CCs accounted for approximately one-third of the total sympathetic restraint during exercise. CHF was then induced by chronic rapid cardiac pacing and characterized by impaired cardiac function, enhanced chemosensitivity, and greater sympathetic restraint at rest and during exercise. In contrast to healthy dogs, CC inhibition in resting CHF dogs produced vasodilation, whereas a similar vasodilatory response was observed during exercise in CHF as compared with healthy dogs. The vasodilation following CC inhibition during exercise and in CHF was abolished with ␣-adrenergic blockade and was absent in healthy exercising animals after carotid body denervation. These results establish an important role for the CCs in cardiovascular control in the healthy animal during exercise and in the CHF animal both at rest and during exercise. Key Words: chemosensitivity Ⅲ sympathetic nervous activity Ⅲ exercise Ⅲ chronic heart failure Ⅲ blood flow D uring exercise, sympathetic vasoconstrictor activity increases, resulting in vasoconstriction in the gut and kidneys and will compete with local vasodilatory influences to constrain locomotor limb blood flow during exercise 1,2 to maintain blood pressure. 3 It is generally assumed that the increased sympathetic nervous activity (SNA) during exercise is caused by feedforward mechanisms such as central command and feedback from muscle metaboreceptors, muscle mechanoreceptors, and/or a resetting of systemic baroreceptors. 3 We propose that the tonic sensory input from the carotid chemoreceptors (CCs) might also be an important source of exercise-induced sympathetic vasoconstrictor activity.The CCs are traditionally thought to be the major oxygen sensors in the body, and their stimulation is assumed to cause a reflex-mediated increase in ventilation. However, CC stimulation also elicits significant increases in sympathetic vasoconstrictor outflow. 4,5 Importantly, the CCs are sensitive to a variety of stimuli in addition to oxygen, including, metabolic acidosis, 6 norepinephrine, 7 potassium, 8 glucose, 9 and angiotensin II, 10 all of which c...