GINSENG total saponins (GTS) injected intracere-broventricularly (i.c.v.) at doses of 0.1–1 μg inhibited the i.c.v. injection stress-induced plasma corticosterone levels in mice. The inhibitory action of GTS was blocked by co-administered NG-nitro-L-arginine methyl ester (L-NAME; 1.5 μg, i.c.v.), an inhibitor of nitric oxide synthase (NOS). Of the ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, 20(S)-Rg3and 20(R)-Rg3injected i.c.v. at doses of 0.01–1 μg, 20(S)-Rg3and Rc significantly inhibited the i.c.v. injection stress-induced plasma corticosterone levels. The inhibitory actions of 20(S)-Rg3and Rc were blocked by co-administered L-NAME (1.5 μg, i.c.v.). These results suggest that GTS, 20(S)-Rg3and Rc may inhibit the i.c.v. injection stress-induced hypothalamo-pituitary-adrenal response by inducing NO production in the brain.