Sho-saiko-to, one of the most frequently prescribed Kampo medicines, is used clinically to treat chronic hepatitis and has shown confirmed clinical efficacy. The present study investigated whether Sho-saiko-to can suppress cytotoxicity and tumor necrosis factor (TNF)-alpha production in endotoxin-treated J774A.1 cells. Sho-saiko-to (10-20 microg/ml) did not affect the proliferation of J774A.1 cells, while a high concentration (50 microg/ml) of Sho-saiko-to induced a slight reduction in cell viability. Treatment with Sho-saiko-to (10-50 microg/ml) significantly inhibited endotoxin (10 microg/ml)-induced cytotoxicity in J774A.1 cells. In addition, Sho-saiko-to (20 microg/ml) suppressed TNF-alpha production by endotoxin (1 microg/ml)-activated J774A.1 cells. These findings suggest that the Kampo prescription Sho-saiko-to suppresses cytotoxicity or TNF-alpha production in macrophages treated with endotoxin and that it may be useful in improving septic shock symptoms. Sho-saiko-to may therefore protect against some of the various disturbances caused by endotoxins through its ability to inhibit TNF-alpha production in septic shock.