S-adenosylmethionine(SAMe) was demonstrated to protect hepatocytes from toxic injury experimental induced in animals and isolated hepatocytes.Thioacetamide(TAA) is a frequently used model hepatotoxin causing in vivo centrilobular necrosis.The aim of our study was to determine the protective mechanisms of SAMe on TAA-induced hepatocyte injury using primary culture.The release of LDH from cells incubated with TAA for 24 h was lowered by contemporary treatment with SAMe for 24 h in a dose depdendent manner.The inhbibitory effect of SAMe on lipid peroxidation paralleled the effect on cytotoxicity.Decrease in mitochondrial membrane potential was prevented too.Attenuation of TAA-induced glutathione(GSH) depletion was determined at the following incubation periods of 48 and 72 h as a potential consequence of increase in GSH production during the continuation of SAMe treatment.