Ginseng saponin administered intraperitoneally to rats induced a significant rise in plasma corticosterone, while it tended to increase plasma glucose and to decrease plasma immunoreactive insulin. Oral or intraperitoneal administration of ginseng saponin increased plasma corticosterone in unanesthetized, pentobarbital-anesthetized or alloxan-diabetes rats. The histamine-induced rise in plasma corticosterone was suppressed by pretreatment with diphenhydramine, whereas the ginseng-induced rise was not. Ginseng saponin decreased rectal temperature while it increased plasma corticosterone. Ginseng-induced corticosterone secretion was superimposed on the basal levels of plasma corticosterone due to fasting and circadian rhythm. Thus ginseng saponin would be a kind of stressful agent and have different features associated with the stimulation of the pituitary-adrenocortical system from several other chemical agents.