The protective effects of antamanide, O-carboxy-methyl-Tyr5-antamanide and of Tyr6-antamanide-monosulfate against phalloidin were tested in perfused rat livers. None of the applied doses was able to inhibit swelling and potassium loss of poisoned livers completely. In the perfused liver antamanide preferentially inhibited swelling but not potassium loss. O-Carboxymethyl-Tyr5-antamanide protected isolated hepatocytes against phalloidin. The different effects of antamanide derivatives in perfused livers and in vivo are discussed.