In rats with chronic neurogenic hypertension induced by sinoaortic baroreceptors denervation (SAD), dl-[3H]norepinephrine (dl-[3H]NE) release, metabolism and vascular response to nerve stimulation were studied in isolated perfused mesenteric arteries. Thirty weeks after SAD, systolic arterial pressure was increased and, in isolated mesenteric arteries, vascular resistance, vascular response to nerve stimulation and responses to exogenous NE were higher in hypertensive than in sham-operated normotensive rats. However, in the isolated mesenteric arteries labeled with dl-[3H]NE, the total increase in radioactivity elicited by nerve stimulation was similar in both SAD and sham-operated groups. Unmetabolized [3H]NE released in mesenteric arteries was higher than that observed in other peripheral noradrenergic tissues (such as cat nictitating membrane, cat spleen, guinea-pig atria) and deaminated glycol 3,4-dihydroxyphenylglycol was the main metabolite of [3H]NE released by nerve stimulation from the mesenteric arteries of both groups. Blockade of prejunctional alpha adrenoceptors with phentolamine increased [3H]NE overflow to the same extent in controls and hypertensive rats. These findings indicate that the negative feedback regulatory mechanism for [3H]NE release mediated by prejunctional alpha adrenoceptors is not affected in chronic neurogenic hypertension. Blockade of postsynaptic alpha receptors by phentolamine reduced the vascular response equally in both groups. In hypertensive rats, a higher fraction of [3H]NE released by nerve stimulation was collected as the extraneuronally formed metabolite 3H-normetanephrine. The results suggest that, in rats with chronic neurogenic hypertension, sympathetic neurotransmission is not altered in the mesenteric arteries. Increased vasoconstrictor response to a given level of sympathetic nerve stimulation and higher resting vascular resistance could, in part, maintain the high blood pressure after 30 weeks of SAD.