Protection against smooth surface dental caries was investigated in fifteen young rhesus monkeys which were immunized subcutaneously with Streptococcus mutans serotype c in Freund's incomplete adjuvant. Monkeys immunized with killed whole organisms developed significantly less caries than control animals. Monkeys immunized with pronase-treated cell walls developed significantly more caries than control animals while monkeys immunized with untreated cell walls showed no such enhancement of caries. Haemagglutinating and complement-fixing antibodies to cell walls and culture supernatant antigens (SN Ag) of S. mutans developed in the sera of all immunized animals to a similar degree. Antibodies to lipoteichoic acid and to an insoluble dextran preparation were found in all immunized animals and showed no relationship to the prevalence of caries. Antibodies to the serotype c polysaccharide were also found in animals immunized with whole cells and pronase-treated cell walls. However, precipitating antibody levels to partially purified antigens I/II and II, derived from SN Ag, but present also in cells, were related to the development of caries. Animals immunized with whole cells and with untreated cell walls developed a brisk antibody response to antigen I/II, while those immunized with pronase-treated cell walls responded more slowly. The results suggest that immunization may induce both caries reduction and enhancement, depending on the antibody response which is developed.