The course of a-amanitin (a-AMA) toxicity in cultured canine and human hepatocytes is divided into 2 phases. The first phase comprises mainly functional cell impairments expressed by inhibition of protein and urea synthesis. The second stage is lethal and is characterized by ongoing necrosis and/ or apoptosis. a-AMA-induced apoptosis in human heptocyte cultures is p53- and caspase-3-dependent. Moreover, a-AMA causes increase in SOD activity, reduction of CAT activity and a significant increase in lipid peroxidation in cells, which may contribute to its severe hepatotoxicity. The findings of the experiments on human hepatocyte cultures demonstrate also, that antidotal efficacy of silibinin, acetylcysteine, ceftazidime or rifamycin was comparable to benzylpenicillin the most often currently used antidote in Amanita phalloides intoxications.