Persistence of serum antibodies after vaccination with group C Neisseria meningitidis polysaccharide was followed in 23 volunteers. Each subject had received a single 50-mug dose of vaccine subcutaneously or intradermally one to five years earlier. Three individuals received a second inoculation eight months after the primary one with no evidence of booster antibody response. Hemagglutination antibody titers rose significantly in 22 of 23 volunteers within two to four weeks of injection; mean titers fell two- to threefold within the first year and then remained stable for four years. Bactericidal tests showed antibody response in 86% of subjects and antibody persistence comparable to that found in the hemagglutination tests. Titers of radioactive antigen-binding antibodies increased significantly in all 22 subjects tested, and after two to four years titers remained at 30% or more of peak concentration. The prolonged duration of antibody responses to polysaccharides in humans suggests that immunity will also persist.