Objectives: Streptococcus mutans is a primary etiologic agent of dental caries in humans, and its most pathogenic trait is sucrose-dependent cellular adherence to tooth surfaces. S. mutans synthesizes water soluble- and/or insoluble-glucans from sucrose by three glucosyltransferases (GTFs), and adheres firmly to tooth surfaces with their cooperation. In addition, the organism synthesizes some glucan binding proteins (Gbps) with no enzymatic activity. Since its sucrose-dependent adherence is mediated by glucans, these Gbps appear to contribute to the virulence of S. mutans. The purpose of this study was to determine the contributions of GbpA and GbpC to dental caries using Gbp-defective mutants. Methods: gbpA (Acc. No. M30945) and gbpC (D85031) genes were amplified by PCR from chromosomal DNA of S. mutans MT8148, and cloned into pGEM-T Easy vector. Next, gbpA and gbpC were inactivated by the insertion of erythromycin and kanamycin resistant genes, respectively, by allelic exchange. These mutants were cultured in 1% sucrose containing BHI broth with [3H] thymidine and [14C-glucose] sucrose, at 37°C for 18 hours and an angle of 30°. The test tubes were then submitted to a vortex, and the amount of adherent cells and insoluble glucan involved with adherence were measured by the incorporation of 3H and 14C, respectively. The caries inducing activities of the Gbp defective mutants and MT8148R were then examined using specific pathogen-free (SPF) Sprague-Dawley rats fed the caries-inducing diet 2000. Results: Cellular and glucan adherence of the GbpC defective mutant were significantly lower than those of its parent strain MT8148 (P < 0.001). Rats carrying the GbpC or GbpA defective mutant showed a significantly lower plaque index, and total caries score than those carrying MT8148R (P < 0.05). Conclusions: These results suggest that GbpA and GbpC participate in the cell adherence and contribute to the cariogenicity of Streptococcus mutans.