Immunodiffusipn studies demonstrated 7–8 precipitinogenic factors in strains of Vibrio cholerae, almost all of which were shared by bacteria of the Inaba and the Ogawa serotype. The endo-. toxin was shown to contain type-specific as well as cross-reactive (group-specific) precipitinogenic determinants. Quantitative inhibition studies by several techniques showed, however, that both homologous and heterologous endotoxin (purified lipopolysaccharide, LPS, with 10–15 per cent nonseparable protein) could give complete antibody inhibition, but for the same degree of inhibition 3- to 43-fold more of the heterologous than of the homologous LPS was needed. By affinity chromatography using columns with LPS coupled to Sepharose beads, it was possible to purify antibodies against V. cholerae LPS and to separate the antibodies against the group-specific and the type-specific endotoxin determinants. Studies by the small bowel loop technique in rabbits showed that antisera and purified anti-endotoxin antibodies protected against both homologous and serotype heterologous experimental cholera. Antibodies to the type-specific endotoxin determinant protected only against homologous infection, whereas the purified group-specific antibodies gave increased resistance against infection with both Inaba and Ogawa bacteria. Subcutaneous immunization of rabbits with formalin-killed vibrios induced a significant level of immunity against homologous infection. Some protection against the heterologous serotype was also observed, which however, was of less magnitude than the homologous immunity.