Maximal activation of Clostridium perfringens epsilon toxin was only achieved by the combined action of trypsin and chymotrypsin. Impure preparations of trypsin, presumably containing small amounts of chymotrypsin were more efficient in activating prototoxin than pure trypsin. Activated toxin was readily absorbed by brain tissue and smaller amounts were possibly absorbed by kidney tissue. Other tissues absorbed only very small amounts of toxin. Injection of mice with toxoid 3 h prior to challenge with toxin increased their resistance 32 times.