To study the effects of matrine (Mat) on lipopolysaccharides (LPS)-induced fatal hepatitis in D-galactosamine (D-GalN)-sensitized mice and tumor necrosis factor (TNF) release from peritoneal macrophages (PMO). METHODS: Mice were pretreated with Mat (10, 50 mg . kg(-1), ip, bid x 3 d), and then;injected ip LPS + D-GalN. Liver injury was assessed by quantifying plasma activity of alanine aminotransferase (ALT) and histopathological examination. The TNF activities in the; supernatants of mouse PMO stimulated with LPS in the presence of Mat (32.5 - 500 mg . L(-1)) were monitored by the L929 target cells lytic assay. RESULTS: Mat pretreatment markedly diminished hepatic injury induced by LPS in combination with D-GalN. Mat inhibited LPS-induced TNF release from mouse PMO in vitro in a concentration-dependent manner. CONCLUSION: Mat protected the D-GalN-treated mice from the development of fatal hepatitis induced by LPS, and inhibited the LPS-induced TNF release from mouse PMO.