While prostaglandin E(2) (PGE(2)) is an established renal vasodilator, studies of prostaglandin EP receptors suggest that it also has vasoconstrictor potential. Prostaglandin E(2) is much more abundant in the medulla than in the cortex, yet likely differences in effects between zones have not been defined. This study is focused on different vascular effects in the cortex and medulla and interaction with the renin-angiotensin system (RAS). In anaesthetized rats, the effects of cyclo-oxygenase blockade and of PGE(2) infused into the renal artery or renal interstitium were examined. Total renal blood flow was measured by ultrasonic renal artery probe, and local perfusion, separately, of the superficial cortex, outer- and inner medulla, as laser-Doppler fluxes. Indomethacin (5 mg kg(-1) i.v.) increased cortical perfusion (by approximately 10%) and decreased medullary perfusion (by approximately 20%). Renal artery infusion of PGE(2) (15-30 microg kg(-1) h(-1)) increased cortical and medullary perfusion only transiently. Previous inactivation of the RAS using losartan or captopril, and background infusion of exogenous angiotensin II, prevented the transient increase and enhanced the subsequent stable decrease in perfusion. Prostaglandin E(2) infused into the medullary interstitium (7-22 microg kg(-1) h(-1)) increased medullary perfusion by 13%, while cortical perfusion decreased by 6%. Misoprostol, an agonist of constrictor EP(3) receptors, decreased perfusion of the cortex and medulla, with both renal artery and medullary interstitial infusion. In conclusion, in rat renal cortex the dominating stable PGE(2) effect is vasoconstriction, most probably mediated by EP(3) receptors and unrelated to activation of the RAS. Prostaglandin E(2) applied to the cortical or medullary interstitium, a natural route for paracrine agents, induces medullary vasodilatation.