Glycopeptides containing polysialic acid units were isolated from human and rat brain and tested for reactivity with antibodies against meningococcal capsules. The polysialosyl glycopeptides bound specifically to horse antiserum against meningococcus group B. The interaction was inhibited by capsular polysaccharides from meningococcus group B but not groups A or C. The capsular polysaccharide of Escherichia coli K1, which is immunochemically similar to the group B polysaccharide, also inhibited binding. These findings could explain the failure to develop efficient vaccines against group B meningococcus or E coli K1 and also suggest that immunological tolerance could be a factor in the pathogenesis of meningitis caused by these bacteria. The presence of the cross-reactive brain component calls for caution in efforts to develop capsular polysaccharide vaccines from these bacteria or the proposed use of passively administered antibodies as immunotherapy of neonatal meningitis.