Intravenous administration of saponin from the root of Panax ginseng (red ginseng) lowered the blood pressure in a dose-dependent manner (10~100 mg/kg B.W) in anesthetized rats. Therefore, experiments were designed to study whether this lowering of blood pressure is associated with the release of endothelium-derived relaxing factor. Rings of thoracic aorta with and without endothelium were suspended for the measurement of isometric tension in organ chamber. All experiments were performed in the presence of indomethacin (10-5 M). Ginseng saponin (10-5~3$ imes$10-4 g/ml) relaxed contractions induced by phenylephrine (10-5 M) in the aorta with endothelium but not in that without endothelium. Treatment of aortic rings with NG_monomethyl-L-arginine (L-NMMA 10-4 M for 30 min), a competive inhibitor of nitric oxide synthase and methylene blue (M.B., 3$ imes$10-7 M for 30 min), an inhibitor of soluble guanylate cyclase, diminished the relaxation induced by ginseng saponin. In thoracic aortic rings from rats treated with ginseng saponin for 2 weeks intraperitoneally, the relaxation to acetylcholine was increased compared with non-ginseng treated rings. These data suggest that red ginseng saponin evokes hypotension and that vascular relaxations induced by red ginseng saponin are inediatpd by release of endothelium-derived relaxing factor.