The effect of topically applied mutanase (α-1-3-glucan, 3-glucanohydrolase) on plaque formation and caries in rats was studied in two experiments. Compounds known to strongly inhibit dental caries when topically applied served as controls in both experiments. The first experiment investigated whether or not and in what frequency of application this agent was effective in reducing dental caries. In addition, effects on the composition of the plaque flora were examined. Because this first trial resulted in a surprisingly high degree of caries protection, the findings were reinvestigated in a second experiment. In addition to crude mutanase, a partially purified enzyme preparation was included. In both studies, it was demonstrated that mutanase was as effective as fluoride or chlorhexidine in reducing the caries incidence on smooth surfaces and in fissures. However, neither the extent of smooth surface plaque nor its bacterial composition was affected by the enzyme preparation. The only conceivable mode of action is, therefore, thought to be a change in the diffusion properties of dental plaque. Furthermore, the pronounced effect of topically applied mutanase may only be explained by the presence of adequate receptors in the oral cavity allowing long-term retention and release of the enzyme