The aim of this study was to determine the contribution of neuropeptide Y (NPY) Y₁-receptors in neurally-mediated reductions in renal medullary perfusion. In pentobarbital anesthetized rabbits, electrical stimulation of the renal nerves (RNS, 0.5-16 Hz) decreased renal perfusion in a frequency-dependent manner. Under control conditions, 4 Hz reduced cortical and medullary perfusion by -85 ± 3% and -43 ± 7%, while 8 Hz reduced them by -93 ± 2% and -73 ± 4%, respectively. After Y₁-receptor antagonism with BIBO3304TF (0.1 mg/kg plus 0.2 mg kg^-1h^-1), RNS reduced perfusion less (by -65 ± 9% and -12 ± 8% at 4 Hz). ₁-Adrenoceptor antagonism with prazosin (0.2 mg/kg plus 0.2 mg kg^-1h^-1) also inhibited RNS-induced reductions in renal perfusion (-80 ± 4 % and -37 ± 10% reductions in the cortex and medulla, respectively, at 8 Hz). When given after BIBO3304TF treatment, prazosin inhibited RNS-induced reductions in cortical and medullary perfusion more profoundly (-57 ± 12% and -25 ± 9% reductions, respectively at 8 Hz). Y₁-receptor- and ₁-adrenoceptor-blockade were confirmed by testing vascular responses to renal arterial NPY and phenylephrine boluses. NPY positive immunolabelling was observed around interlobular arteries, afferent and efferent arterioles and in the outer medulla. In conclusion, Y₁-receptors and ₁-adrenoceptors contribute to RNS-induced vasoconstriction in the vessels that control both cortical and medullary perfusion. Consistent with this, NPY immunostaining was associated with blood vessels that control perfusion in both regions. There also seems to be an interaction between Y₁-receptors and ₁-adrenoceptor mediated neurotransmission in the control of renal perfusion.