Antibodies to Escherichia coli J5, a uridine 5'-diphosphate-galactose epimerase-less mutant of E. coli 0111, neutralized meningococcal endotoxemia from all three major capsular serogroups. We chose the dermal necrosis of the local Shwartzman phenomenon and the renal cortical necrosis of the general Shwartzman phenomenon as assays because these are the hallmarks of meningococcemia, and because meningococcal lipopolysaccharide (LPS) is a uniquely potent cause of dermal purpura and necrosis. Meningococcal antisera raised against LPS from MGC A, B, and C also provided good protection against endotoxemia from the homologous capsular groups, but it was inconsistent against the heterologous serogroups. The superiority of J5 antibodies (purified IgG as well as antiserum) is probably due to the fact that J5 LPS contains only the endotoxin core. Consequently, immunization with this mutant stimulates production of antibodies to core LPS without interference by the "0" antigenic determinants of the side chains. These observations indicate that the endotoxin core is the toxic moiety of meningococcal LPS, that the core LPS of meningococcus (MGC) is immunologically similar to enteric LPS, and that the antigenically variable "0" side chains of MGC LPS interfere with antibody production against the common core. They also suggest that antibodies prepared against this E. coli mutant could interrupt the devastating course of meningococcal endotoxemia in man, regardless of the capsular serogroup of the infecting strain.