A preclinical method for the evaluation of antibacterial agents for use against dental plaques associated with caries and periodontal disease is proposed. The method is applicable to screening agents and to defining, in vitro, the minimal conditions required for maximal antiplaque effect. As a model of antiplaque agents, chlorhexidine was assessed in vitro against preformed plaques of microorganisms conducive to dental caries and periodontal disease. The agent was bactericidal to plaques of nine strains of Streptococcus mutans and one strain of Actinomyces viscosus when used in a single treatment for 20 min at 2 × 10 −1 %, in two 2-min treatments on the same day, or in daily 2-min treatments at this same concentration. Using the last of these experimental conditions, we then tested chlorhexidine in vivo by topical application to the maxillary teeth of infected hamsters and found it to be effective in controlling plaques of S. mutans and A. viscosus .