The long-term objective of this research is to characterize the relationship between bacteria indigenous to the mouth andthe immune system. The specific aim is to test the hypothesis that resistance or susceptibility to cariogenic bacteria is determined by the dynamic balance between salivary antibodies to Streptococcus mutans and serum antibodies to autologous antigens on salivary immunoglobulins. Laboratory rats will be used to (1) study the effects of dose and duration of enteric exposure to S. mutans on the production of antibodies in saliva and serum and on the production of serum anti-antibodies, and (2) to assess the effect of the immune network on resistance to dental caries. A quantitative ELISA and an immunoblot assay will be used to measure quantities and specificities of antibodies and to identify isotypes of acquired antibody. IgA and IgG in saliva will be separated by means of Staphylococcus protein A. Functional interactions of salivary IgA and serum anti-idiotype will be assessed with a bacterial aggregation assay. The hypothesis predicts that, in accordance with preliminary observations made in rats and humans, chronic exposure to high doses of S. mutans will lead to the dominance of non-specific salivary and serum antibodies and the production of high levels of antigen-specific anti-antibodies in serum. This state will correlate with small bacterial aggregates, little interaction between salivary and serum antibodies and with susceptibility to dental caries. The hypothesis also predicts that low or intermittant exposure to S. mutans leads to coexistance of specific salivary S. mutans antibodies and serum anti-antibodies. This state will correlate with the formation of large bacterial aggregates, interaction between salivary and serum antibodies and with resistance to dental caries. Information about the relationship between oral/intestinal microorganisms and the immune network may contribute to a better understanding of secretory and serum immune defense systems and of chronic diseases of mucosa in general. These experiments offer a new direction in research in dental immunology.