We tested the hypothesis that activation of angiotensin type 2- (AT_2-) receptors, by both exogenous and endogenous angiotensin II, modulates neurally-mediated vasoconstriction in the renal cortical and medullary circulations. Under control conditions in pentobarbital anesthetized rabbits, electrical stimulation of the renal nerves (RNS; 0.5-8 Hz) reduced renal blood flow (RBF; -88 ± 3% at 8 Hz) and cortical perfusion (CBF; -92 ± 2% at 8 Hz) more than medullary perfusion (MBF; -67 ± 6% at 8 Hz). Renal arterial infusion of angiotensin II, at a dose titrated to reduce RBF by ~40-50% (5-50 ng kg^-1min^-1) blunted responses of MBF to RNS, without significantly affecting responses of RBF or CBF. Subsequent administration of PD123319 (1 mg/kg plus 1 mg kg^-1h^-1) during continued renal arterial infusion of angiotensin II did not significantly affect responses of RBF or CBF to RNS, but enhanced responses of MBF so that they were similar to those observed under control conditions. In contrast, administration of PD123319 alone blunted responses of CBF and MBF to RNS. Subsequent renal arterial infusion of angiotensin II in PD123319 pre-treated rabbits restored CBF responses to RNS back to control levels. In contrast, angiotensin II infusion in PD123319 pre-treated rabbits did not alter MBF responses to RNS. These data indicate that exogenous angiotensin II can blunt neurally mediated vasoconstriction in the medullary circulation through activation of AT₂-receptors. However, AT₂-receptor activation by endogenous angiotensin II appears to enhance neurally-mediated vasoconstriction in both the cortical and medullary circulations.