Antibodies to whole cells of Streptococcus mutans were examined in 108 subjects by a solid-phase radioimmunoassay and quantified by reference to isotype-specific affinity-purified antibodies. Serum antibodies of each isotype were present in all subjects examined. The mean concentration of serum antibodies to S. mutans was calculated as about 84 micrograms/ml of IgG (range 33-140 micrograms/ml), 26 micrograms/ml of IgA (range 12-43 micrograms/ml) and 9 micrograms/ml of IgM (range 4-15 micrograms/ml). The mean antibody values accounted for about 0.7, 1 and 0.8% of the total IgG, IgA, and IgM, respectively. Overall the antibody binding to whole cells of S. mutans accounted for about 0.8% of the total immunoglobulin. Inhibition experiments using a variety of purified cell wall antigens revealed that the binding of antibodies to whole cells could be inhibited by about 30% with a purified protein antigen (SA I/II) and with glucosyltransferase (GTF), by 25% with c polysaccharide and by 16% with lipoteichoic acid. The protein antigens GTF and SA I/II appear to be major immunogenic cell wall antigens, but natural antibodies in man that bind to S. mutans whole cells have been induced by several antigens, some of which are specific to S. mutans and some of which are shared with other Gram-positive bacteria.