Intrarenal infusion of adenosine induces transient renal vasoconstriction followed by sustained renal vasodilation. The purpose of this study was to elucidate the role of endothelium-derived relaxing factor (EDRF) in renal hemodynamic actions of adenosine in anesthetized dogs. Intrarenal arterial infusion (i.r.a.) of EDRF synthesis inhibitors, L-NG-monomethyl-arginine (160 micrograms/kg/min) and L-NG-nitro-arginine (80 micrograms/kg/min), attenuated acetylcholine-induced increases in renal blood flow and renal vascular resistance was increased. Renal vasoconstriction elicited by adenosine (100 nmol/min i.r.a.) was potentiated and the duration was prolonged by pretreatment with either EDRF synthesis inhibitor. Adenosine infusion significantly decreased glomerular filtration rate (GFR) by more than 30% in the presence of EDRF inhibitors, whereas GFR remained unchanged by adenosine in the absence of EDRF synthesis inhibitors. L-arginine (2 mg/kg/min i.r.a.) significantly reversed the potentiation of adenosine-induced renal vasoconstriction and adenosine-induced reduction in GFR elicited by pretreatment with EDRF synthesis inhibitors. On the other hand, the adenosine A2 selective agonist, CGS 21680C (0.37 nmol/kg/min i.r.a), elicited monophasic renal vasodilation and this effect on renal blood flow was unaffected by EDRF inhibitor. These results suggest that arginine-derived EDRF is involved in the renal vascular action of adenosine. In the present experimental setting, we obtained no evidence for the interaction between arginine-derived EDRF and CGS 21680C-activated A2 adenosine receptor in renal vascular beds.