The effects of angiotensin II (ANG II) and norepinephrine (NE) on total renal blood flow (RBF) were studied in rats fed an essential fatty acid (EFA)-deficient diet. EFA deficiency was employed, as an alternative to the use of cyclooxygenase inhibitors, to investigate the influence of arachidonic acid metabolites on rat RBF. Intrarenal arterial (ira) bolus doses of ANG II (2-16 ng) and NE (25-100 ng) elicited significantly greater decrements in RBF and increments in renal vascular resistance in anesthetized Sprague-Dawley rats fed EFA-deficient diets than in control rats, which were fed EFA-adequate diets. Indomethacin (5 mg/kg iv) enhanced the vasoconstrictor responses to ANG II and NE in rats fed the EFA-adequate diet but not in rats fed the EFA-deficient diet. In rats fed regular laboratory chow the renal vasoconstrictor response to ANG II was potentiated after the administration of either indomethacin or naproxen (5 mg/kg iv). Methacholine and prostaglandins E2 and I2 caused dose-related renal vasodilatation when injected (ira) over the dose range of 10-40 ng in rats fed either the EFA-deficient or -adequate diets. The increased responsiveness of the renal vascular bed to ANG II and NE in rats fed EFA-deficient diets was not attributable to reduced vasodilator efficacy. Collectively, these results suggest that the net effect of endoperoxide products of arachidonic acid metabolism attenuates the vasoconstrictor influences of exogenous ANG II and NE in the intact rat kidney.