This study sought to quantitate the response of late complement component-deficient (LCCD) individuals to the meningococcal vaccine, to examine antibody persistence, and to investigate the contribution of these antibodies to meningococcal killing in complement- and phagocyte-dependent bactericidal assays. The mean concentration of antibody to group A and C capsular polysaccharide after vaccination was similar in 8 LCCD, 11 family members, and 7 unrelated normal individuals. LCCD individuals had a greater percentage decline in antibody concentration to group C polysaccharide and had lower concentrations of antibody to group Y polysaccharide 2.0-2.5 years after vaccination than did normal and heterozygous deficient persons. Antibody to subcapsular antigens was minimally effective in mediating complement-dependent killing and had no effect in the opsonophagocytic assay. In contrast, antibody to capsular polysaccharide promoted meningococcal killing in both assays. These data support vaccination as a preventive measure in LCCD individuals and lend credence to the idea that these individuals are critically dependent on capsular antibody for protection against meningococcal disease.