The present experiments were carried out to investigate the mechanisms of anti-inflammatory action of Shosaiko-to. The intraperitoneal administration of Shosaiko-to to rats produced increases in corticosterone level in the serum, adrenocorticotropine (ACTH) level in the plasma and cyclic adenosine monophosphate contents in the pituitary and adrenal gland. The elevations of serum corticosterone and plasma ACTH level induced by Shosaiko-to were inhibited by the treatment with dexamethasone (2.5 mg/kg, i.p.). Basal and ACTH-induced secretions of corticosterone from adrenal slices were not influenced by Shosaiko-to in vitro. Although Shosaiko-to did not increase plasma ACTH level in adrenalectomized rats, the action of Shosaiko-to to increase plasma ACTH level was observed in adrenalectomized rats which was administered corticosterone to maintain normal corticosterone level in the serum. Shosaiko-to produced a marked inhibition in exudate volume and leukocyte number in carrageenin-induced pleurisy of rats. Also chemotaxis of rat polymorphonuclear leukocytes and histamine release from rat peritoneal mast cells were suppressed by Shosaiko-to in vitro. Of the constituent crude drugs, Bupleuri Radix, Scutellariae Radix, Glycyrrhizae Radix and Ginseng Radix induced a marked elevation of serum corticosterone level. The histamine release from rat peritoneal mast cells was suppressed by Bupleuri Radix and Glycyrrhizae Radix. These results suggest that Shosaiko-to may produce an antiinflammatory effect by at least two mechanisms in rats. One is a stimulating action on the pituitary-adrenocortical function, and the other is direct inhibitions of histamine release from rat peritoneal mast cells and chemotaxis of polymorphonuclear leukocytes.