Antibodies to S. salivarius, S. sanguis, and S. mutans cells and to glucosyltransferases (GTF) prepared from these micro-organisms were measured in the sera of 133 infants and children by enzyme-linked immunosorbent assay (ELISA). IgG antibody activity to each cell type and GTP was present at birth (presumably derived from maternal transfer) and declined significantly thereafter. IgG antibody levels to S. salivarius and S. sanguis were next detected in young children (2 to less than 3 yr group). However, an increase in IgG antibody to S. mutans cells was not seen until children were older (4 to less than 8 yr group), possibly reflecting the later colonization of this organism. In contrast, IgG antibody to GTF of all three streptococcal species remained at low levels throughout the first four years of life. IgG antibody to S. mutans GTF was then the first to appear (4 to less than 8 yr group). Serum IgA antibodies to all GTFs were not detected until after this time. Fifteen sera were used to develop IgG immunoblots with the GTF antigens. Some positive sera (7/12) demonstrated reaction(s) with GTF from each of the three streptococcal species. Individual sera showed IgG antibody bonds to GTF from several serotypes of the mutans streptococci. No immunoblot reaction was observed with GTF and sera (3) from the four-to-seven-year and younger age groups. These results indicate the presence of serum antibody to bacteria and bacterial products associated with plaque formation very early in life and during and after the pre-adolescent years. The potential exists for this serum antibody to modulate bacterial colonization or accumulation in the oral cavity.