The effects of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the synthesis of the endothelium-derived relaxing factor nitric oxide, were studied in two isolated perfused vascular beds: the rat mesenteric arterial bed and the hepatic arterial bed of the rabbit liver. The tone of both preparations was raised with noradrenaline (10 and 30 microM for rabbit and rat preparations, respectively). In both preparations, L-NAME (30 microM) significantly attenuated vasodilator responses to the endothelium-dependent vasodilator acetylcholine, but enhanced responses to sodium nitroprusside (a direct smooth muscle dilator). The evidence supports the view, previously established from work carried out in isolated vessels, that in addition to acting as an inhibitor of nitric oxide, L-NAME enhances the responsiveness of smooth muscle to direct relaxation by nitrovasodilators.