AbstractWe have shown that a traditional Chinese medicine, Xiao-chai-hu-tang (Japanese name: Shosaiko-to) augments natural killer (NK)1activity in mice. The maximum augmentation of NK activity in the peripheral blood and liver was observed at 12 hr after administration of Shosaiko-to. NK activity was augmented by Shosaiko-to dose-dependently. The augmentation became significantly positive at a dose of 500 mg/kg, and the maximum effect was observed at a dose of 1000 mg/kg. The augmentation of NK activity appeared at first in the liver from 6 hr after administration of Shosaiko-to and became detectable later in the peripheral blood from 12 hr after the administration. Activation of NK cells by Shosaiko-to may occur in the liver and subsequently the activated NK cells may be supplied to the peripheral blood. Changes in percentages of cell surface markers (asialo GM1, CD3, CD4, CD8) after Shosaiko-to treatment were hardly detected, but augmentation of NK activity induced by Shosaiko-to was abrogated by anti-asialo GM1 antibody treatment before the cytotoxicity assay. In addition, cytotoxic activity to P-815 target cells was not detected in Shosaiko-to treated mice. Augmentation of NK activity by Shosaiko-to is probably mediated by functional activation of classical NK cells of asialo GM1+phenotype.These results suggest that augmentation of NK activity in the liver is one of mechanisms involved in clinical efficacy of Shosaiko-to in patients with virus chronic hepatitis.