Rats (COBS/CD) provided Formalin-killed Streptococcus mutans 6715, C211 in their drinking water (108 to 109 equivalent colony-forming units [CFU] per ml) had high levels of specific antibodies in saliva, colostrum, and milk. Rats provided a lower concentration of S. mutans antigen (107 CFU per ml) in water had agglutinin titers in secretions that were similar to those in controls. Gnotobiotic rats provided S. mutans antigen in food (107 to 108 equivalent CFU per g of diet) manifested a secretory immune response as evidenced by the presence of specific immunoglobulin A antibodies in saliva, colostrum, and milk. Gnotobiotic rats provided a higher concentration of antigen (109 CFU per g) in food had levels of specific antibodies in their secretions that were similar to those in controls. No significant antibody activity to S. mutans was observed in sera of any group of animals. Furthermore, the presence of specific salivary immunoglobulin A antibodies in gnotobiotic rats correlated with a reduction in the level of plaque, numbers of viable S. mutans in plaque, and levels of S. mutans-induced dental caries. This paper discusses the importance of antigen dosage for induction of a secretory immune response that is protective against S. mutans-induced dental caries.