Evidence suggests that angiotensin II (All) can modulate neuroeffector responses in the vasculature of spontaneously hypertensive rats (SHR). Included in this modulation is an action of All in facilitating release of neurotransmitter from sympathetic nerves by a mechanism involving prejunctional angiotensin receptors. In addition, AH may be a substrate for the carrier processes that operate within sympathetic nerves. Therefore, we examined the influence of All on the responses to sympathetic nerve stimulation in the isolated perfused mesenteric vascular bed preparation and determined whether All was incorporated into neuronal tissue in blood vessels. AII (10-8) shifted the frequency-response curves to the left, and this shift was reversed with addition of the All receptor type 1 (AT1) antagonist losartan (10-6M). All uptake into mesenteric artery, thoracic aorta, kidney, and skeletal muscle was determined in tissues taken from SHR and normotensive Wistar-Kyoto rats (WKY). Additional tissues were taken from animals that had been subjected to chemical sympathectomy with 6-hydroxydopamine (6-OHDA). Although All accumulation was evident in all tissues examined, in no case was this accumulation diminished by 6-OHDA treatment. Subsequent studies using segments of kidney and skeletal muscle demonstrated that a large proportion of AH accumulation was temperature sensitive and was also sensitive to the metabolic inhibitor 2–4-dinitrophenol (DNP 10-3M). The results confirm the role of All in potentiating the responses to sympathetic nerve stimulation through a process involving AT1 receptors, but this process is not associated with neuronal accumulation of the peptide.