Human antibodies to bacterial polysaccharides consist primarily of IgG and are largely restricted to the IgG2 subclass in adults. We examined the ontogeny of the IgG subclass response to pneumococcal polysaccharide type 3 to determine if the poor response of infants to immunization with polysaccharide antigens is due to a diminished capacity to form this subclass of antibodies. Sera from 33 patients aged 2 months to 25 years who had previously been shown to respond to polyvalent pneumococcal polysaccharide vaccine by producing IgG antibodies, were assayed for pneumococcal type 3 specific antibodies of the IgG1, IgG2, IgG3, or IgG4 subclass. IgG1 antibodies to pneumococcal polysaccharide type 3 were uniformly low in all age groups. In contrast, IgG2 antibody activity was lowest in children less than the age of 2 years (170 +/- 20 ng/ml), but rose progressively in the age group 2-5 years (210 +/- 40 ng/ml), 5-10 years (330 +/- 30 ng/ml), and over the age of 10 (390 +/- 30 ng/ml) (differences significant at P less than 0.0005 by ANOVA). Thus, even in infants, pneumococcal polysaccharide responses are confined largely to the IgG2 subclass. Our findings are consistent with the hypothesis that purified bacterial capsular polysaccharide antigens preferentially activate IgG2-committed B cell clones at all ages.