Summary The pyrogenicity of endotoxin which had been diminished by incubation with papain was restored by treatment of the inactive complex with pronase and ethanol, indicating that a hydrolytic cleavage of the endotoxin molecule had not occurred. In addition, it was shown that the reduction of the second fever peak in papain-inactivated endotoxin could be explained on the basis of a normal dose-response phenomenon. These findings suggest that there is no disagreement between the inactivation of a purified endotoxin by papain and the observed correlation of the biological activity of endotoxin with the polysaccharide portion of the molecule.