The effects of trehalulose, a structural isomer of sucrose, and a syrup (TP syrup) rich in trehalulose and palatinose on caries development were examined in specific pathogen-free Sprague-Dawley rats. Streptococcus mutans MT8148R and Streptococcus sobrinus 6715 fermented the syrup which resulted in acid production, while both strains were found not to utilize trehalulose. Furthermore, trehalulose did not serve as a substrate for glucosyltransferases of these mutans streptococci to synthesize water-insoluble glucan, and it inhibited the sucrose-dependent adherence of mutans streptococci to a glass surface. Although trehalulose induced no significant dental caries in specific pathogen-free rats infected with either MT8148R or 6715, TP syrup was found to induce significant but low dental caries. Furthermore, replacement of the dietary sucrose content with trehalulose resulted in a significant reduction of caries development in rats infected with strain 6715.