The protective effect of two silybin derivatives against phalloidin was tested in isolated rat livers, perfused with an erythrocyte free medium. Both liver swelling and potassium loss were examined for the evaluation of antagonism. Liver swelling and potassium loss were markedly decreased when silybin hemisuccinate was added to the perfusion medium before the application of phalloidin. In contrast, the protective effect of this compound was minimal after the mushroom toxin was partially absorbed by the liver. The protective efficiency of a dimer derivative (disilybin) was much greater than that of the monomer product. The binding of both derivatives in the liver cannot be very strong because the protective effect mainly could be washed out by a single change of the perfusion medium. Spectroscopical studies on isolated hepatocytes indicate that silybin inhibits the interaction of phalloidin with the cell surface.