High dose penicillin-G has been found empirically to be effective against liver cell damage in amanita mushroom poisoning. We have recently found that betalactam antibiotics inhibit eukaryotic DNA polymerase-alpha, penicillins being more active than cephalosporins, and this may explain the antagonistic effect of penicillin-G against amanitin toxicity. Preliminary experiments in liver cell cultures and in mice are summarized, as well as first clinical experience pointing to the possibility that cephalosporins may be more effective against amanita mushroom toxicity than penicillin-G.