Actinomyces are predominant oral bacteria; however, their cariogenic potential in terms of acid production and fluoride sensitivity has not been elucidated in detail and compared with that of other caries-associated oral bacteria, such as Streptococcus. Therefore, this study aimed to elucidate and compare the acid production and growth of Actinomyces and Streptococcus in the presence of bicarbonate and fluoride to mimic conditions in the oral cavity. Acid production from glucose was measured by pHstat at pH 5.5 and 7.0 under anaerobic conditions. Growth rate was assessed by optical density in anaerobic culture. Although Actinomyces produced acid at a lower rate than did Streptococcus, their acid production was more tolerant of fluoride (ID acid production 50 ¼ 110-170 ppm at pH 7.0 and 10-13 ppm at pH 5.5) than that of Streptococcus (ID acid production 50 ¼ 36-53 ppm at pH 7.0 and 6.3-6.5 ppm at pH 5.5). Bicarbonate increased acid production by Actinomyces with prominent succinate production and enhanced their fluoride tolerance (ID acid production 50 ¼ 220-320 ppm at pH 7.0 and 33-52 ppm at pH 5.5). Bicarbonate had no effect on these variables in Streptococcus. In addition, although the growth rate of Actinomyces was lower than that of Streptococcus, Actinomyces growth was more tolerant of fluoride (ID growth 50 ¼ 130-160 ppm) than was that of Streptococcus (ID growth 50 ¼ 27-36 ppm). These results indicate that oral Actinomyces are more tolerant of fluoride than oral Streptococcus, and bicarbonate enhances the fluoride tolerance of oral Actinomyces. Because of the limited number of species tested here, further study is needed to generalize these findings to the genus level.Key words acid production, bicarbonate, fluoride, oral Actinomyces.Similarly to Streptococcus, Actinomyces are predominant oral bacteria (1) that are detected from dental plaque biofilm of healthy tooth surfaces and oral mucosa (2). This bacterium is also frequently isolated from periodontitis lesions (3-6) and root surface caries (7-10), suggesting that it is associated with various oral diseases. In particular, its role in the causation of root surface caries has been a focus (7,11). The importance of this research has further been supported by recent comprehensive analyses of microbiota in root surface caries lesions (12)(13)(14).The main cariogenic factor is acid production by carbohydrate metabolism. Actinomyces species can degrade List of Abbreviations: A., Actinomyces; ATP, adenosine-5 0 -triphosphate; EMP, Embden-Meyerhof-Parnas; G3PDH, glyceraldehyde-3-phosphate dehydrogenase; HF, hydrogen fluoride; ID acid production 50, 50% inhibitory dose of fluoride on acid production; ID growth 50, 50% inhibitory dose of fluoride on growth; LDH, lactate dehydrogenase; NAD, nicotinamide adenine dinucleotide (oxidized form); NADH, nicotinamide adenine dinucleotide (reduced form); OD, optical density; PEP, phosphoenolpyruvate; PEP-PTS, phosphoenolpyruvate-dependent phosphotransferase; PFL, pyruvate formate-lyase; PPB, potassium phosphate b...