G2m(23), an allotype on IgG2 molecules, is detected in sera of about two of three Caucasians. Adults who are homozygous for G2m(23) have IgG2 antibody responses to types 14 and 18C pneumococcal polysaccharides fourfold higher than those of homozygous-negative subjects. Adults homozygous for G2m(23) also show higher IgG2 antibody responses to vaccination with Haemophilus influenzae type b (Hib) polysaccharide. Furthermore, adults heterozygous for G2m(23) show IgG2 antibody responses intermediate between responses of those homozygous-positive and homozygous-negative. In contrast, the magnitude of the IgG1 antibody responses of adults to Hib polysaccharide was similar irrespective of G2m(23) genotype status. The magnitude of the IgG antibody responses of children vaccinated with Hib polysaccharide is not affected by G2m(23) status, in part because the IgG subclass responses of children to this antigen are restricted to IgG1. Also, children show no consistent associations between G2m(23) allotype status and the risk of acquiring Hib disease or the risk of Hib vaccination failure.