In the present study, we characterized the angiotensin II (AII)-induced relaxations in the phenylephrine- precontracted rabbit mesenteric arteries with endothelium. 1) AII-induced relaxation was consistently observed in the rabbit mesenteric arteries with and without endothelium, but not in the aortic segment with endothelium. 2) AII-induced endothelium-dependent relaxation was markedly inhibited by Nw-nitro- L-arginine (L-NNA, 100 ㄍM), methylene blue (10 ㄍM) and LY83583 (10 ㄍM), respectively. 3) Inhibition of cyclooxygenase with indomethacin (10 ㄍM) strongly decreased the vasorelaxant response to AII irrespective of the presence of endothelium. 4) 7-Ethoxyresorufin (1 ㄍM) and clotrimazole (1 ㄍM), inhibitors of cytochrome P-450-dependent arachidonic acid metabolism, greatly attenuated the vasodilator response to AII. 5) Carbacyclin, arachidonic acid and prostaglandin F2α (PGF2α) caused concentration-dependent relaxations in the mesenteric artery with endothelium, which were inhibited by L-NNA and methylene blue. 6) AII and PGF2α significantly stimulated cyclic GMP formation in the mesenteric arteries with endothelium, which was inhibited by L-NNA and methylene blue, respectively. 7) AII enhanced synthesis of PGF2α and 6-keto PGF1α from the arterial segments with endothelium, which was inhibitable by indomethacin, but not by L-NNA. In conclusion, the vasorelaxant responses to AII of the rabbit mesenteric artery with endothelium are subserved by arachidonic acid and its metabolites produced via activation of cyclooxygenase and cytochrome P-450 enzyme as well as by nitric oxide.