Mesenteric arteries are densely innervated by perivascular nerves, the density of the innervation increasing towards the resistance arteries. Perivascular nerves are important regulators of vascular tone and consequently blood pressure. Sympathetic nerve activity has been shown to be increased in patients with hypertension and perivascular sensory nerves function is increased in some animal models of hypertension and decreased in others. Perivascular sensory nerves have been shown to possess potent vasodilating properties in vitro. However, little is known about the function of the perivascular sensory nerves in vivo. Male Wistar rats (10-12 weeks old; n=72) were anesthetized with isoflurane (3%) before subcutaneous injection of ketamine (3 mg kg-1) and xylazine (0.75 mg kg-1) or intraparietal injection of pentobarbital (60 mg kg-1). After a laparotomy, the small intestine was exteriorized and a 2nd order mesenteric artery segments isolated in an organ bath and the vessel visualized after minimal removal of perivascular adipose tissue. The diameter and flow changes to perivascular nerve stimulation (PNS) or drugs, were recorded with intravital microscopy and laser speckle imaging (LSI) respectively. PNS induced vasodilation was induced in arteries incubated with endothelial cell blockers (100µM L-NAME, 3µM indomethacin, 1µM TRAM-34 and 50nM apamin) and preconstricted with 1µM U46619 in the presence of 140µM suramin and 1µm prazosin. The vasodilation was sensitive to: 1µM tetrodotoxin, 1 µM atenolol and 5µM guanethidine. The NPY Y1 antagonist BIBP3226 (0.3µM) increased the vasodilation; the CGRPR antagonist BIBN4096bs (1 µM) caused a small decrease in vasodilation while atenolol inhibited a large part particularly at the high frequencies (fig. 1). Increasing the extracellular potassium concentration to 20 mM caused vasodilation which was sensitive to 1µM BIBN4096 and the contraction to 30mM potassium was potentiated by BIBN4096bs. Atenolol – but not BIBN4096bs – increased contraction to PNS. PNS induced nerve-mediated vasodilation was predominantly β1-adrenoceptor dependent since it was TTX, guanethidine, and atenolol sensitive. A minor neurogenic CGRPergic vasodilation was observed, but only after blocking NPY-Y1 or after increasing extracellular potassium.