In the isolated frog muscle, the proteinaceous venom extracted from jellyfish (genus Aurelia) produced 1) a complete and irreversible block of indirectly and directly elicited muscle twitch and 2) an irreversible depolarization of the muscle membrane. This venom-induced depolarization was effectively reversed or prevented by the substitution of choline for sodium in Ringer solution, but not by the introduction of tetrodotoxin (TTX), a sodium channel blocker. The mechanism of muscle membrane depolarization appears to involve probably an increase in membrane permeability to sodium ion as shown by the decrease in membrane resistance. These results suggest that the venom forms a pore which has sodium selectivity or activates a TTX-insensitive sodium channel which is different from the known sodium channel.