To determine the mechanisms by which Hange-shashin-to (TJ-14) reduces prostaglandin E2 (PGE2) levels, the effects on blood corticosterone levels were examined in vivo and the effects on cyclooxygenase (COX) activity in vitro assessed. TJ-14, orally administered to rats at dose levels between 125 and 1000 mg/kg, caused a dose-dependent increase in blood corticosterone levels. We also showed that Glycyrrhizae Radix and Ginseng Radix, constituents of TJ-14, are involved in the increase in blood corticosterone. The activity of COX-1 was not inhibited by TJ-14 even at a dose of 1000 microg/ml, while COX-2 was inhibited at dose levels between 10 and 1000 microg/ml. The constituents Scutellariae Radix, Glycyrrhizae Radix and Coptidis Rhizoma were believed to be involved in COX-2 inhibition. These results suggest that the effect of TJ-14 in decreasing PGE2 is partially mediated by corticosterone and inhibition of COX-2.