Summary A substantial loss in the ability of endotoxin to be precipitated by homologous antibody occurs following incubation with Fraction IV1 derived from normal human serum by cold ethanol fractionation. Evidence is presented that this loss in serologic reactivity is not associated with release of the major determinant sugar, per se. Rather, immunodiffusion analysis revealed the dispersion of a major antigen, with formation of a more rapidly migrating component. The latter was shown to form a line of identity with the O polysaccharide hapten.