The responsiveness of central nervous system α2-adrenergic receptors in the neural control of renal function was compared in conscious spontaneously hypertensive rats (SHR) and normotensive Wlstar-Kyoto rats (WKY) on normal or high sodium intake (3–4 weeks of 1% NaCl for drinking). The responsiveness of central aradrenergk receptors was determined by comparing among groups the dose-response curves for the effects of cumulative intracerebroventricular injections of guanabenz (5, 25, and 125 μg) on changes in mean arterial pressure, renal sympathetic nerve activity, and urinary sodium excretion. Guanabenz altered mean arterial pressure similarly in SHR on normal or high sodium intake and in WKY on normal or high sodium intake. High sodium intake shifted the guanabenz-renal sympathetic nerve activity and guanabenz-urinary sodium excretion dose-response curves to the left in SHR and to the right in WKY. The dose-response curves between SHR and WKY on normal sodium intake were similar. Surgical renal denervation or pretreatment with an α2-adrenergic receptor antagonist (rauwolscine, 30 fig i.c.v.) attenuated the ability of guanabenz to inhibit renal sympathetic nerve activity or increase urinary sodium excretion in SHR and WKY on either normal or high sodium intake. We conclude that the responsiveness of central nervous system α2-adrenergic receptors regarding the neural control of renal function is increased by high sodium intake in conscious SHR, but not in conscious normotensive WKY.