Because of extensive industrial, medical and dental uses of weak acids, most indificuals are daily subjected to a wide variety of these agents. For example, in medicine, indomethacin and aspirin are routinely used in the treatment of rheumatoid arthritis and similar inflammatory diseases. The food industry utilizes large amounts of sorbic acid and benzoic acid as preservatives, acidulants and antifungal agents. Fluoride, the major anticaries agent, also is a weak acid. The effectiveness of weak acids as possible antimicrobial agents (except in the case of fluoride) has received little attention. One major aim of the proposed work is to determine if weak acids commonly employed in medicine and the food industry may be present in sufficient amounts in plaque and saliva to affect common plaque and salivary bacteria. Thus the initial phases of this research project will be concerned with the collection and processing saliva andplaque to assay levels of sorbic acid, benzoic acid, indomethacin and salicylate. Samples will be compared between control subjects and patients undergoing indomethacin and salicylate therapy for the treatment of inflammatory diseases. The second major aim is to determine which oral microorganisms are most inhibited by these compounds and what are the specific modes of action. The planned in vitro tests are designed to determine the sensitivity of common oral bacteria to these same agents as well as to similar acting compounds including fluoride. These experiments involve the testing of weak acids over a range of acid concentrations and pH values. Furthermore, a series of experiments is described which will measure the effects of specific weak acids on important cell functions such as growth, acid production, maintenance of proton motive force, solute transport and export of enzymes. It is my long-term hope that if weak acids are found to concentrate in saliva or plaque and can be shown to produce inhibition of oral bacterial pathogens that they as additives in foods, medicine and by topical application may provide a safe and effective way of reducing dental disease.