To study central and peripheral mechanisms that regulate the level of circulating renin during activation of the carotid sinus baroreflex, both carotid sinuses were isolated and perfused at constant flow in chloralase-anesthetized dogs. Sinus pressure was controlled by an adjustable reservoir while systemic pressure was stabilized using an external chamber. Arterial renin activity, measured by radioimmunoassay, was increased during sinus hypotension only if systemic pressure was held constant. The renin response was eliminated by either sinus or renal denervation. Administration of propranolol (iv) or phentolamine directly into the renal artery totally blocked the increase in renin during activation of the reflex. Perfusion of a beta-adrenergic blocker (propranolol) or an alpha-adrenergic blocker (phentolamine) through the third and fourth cerebroventricles had no effect on the increase in renin during sinus hypotension, whereas centrally administered clonidine, and alpha-agonist, blocked the response. We conclude that the sinus reflex arc affecting renin release involves not only activation of peripheral alpha- and beta-adrenergic receptors in the kidney but also inhibition of central alpha-adrenergic receptors. No evidence for central beta-involvement was found.