A new method, the Plaque Glycolysis and Regrowth Method (PGRM), is described for the evaluation of antimicrobial effects on plaque metabolism in vivo. The method relies on the experimental observation that in vivo sampled dental plaques, collected from different quadrants of the dentition, produce equivalent rates of metabolic activity and regrowth when similarly dispersed and normalized into incubation media. In applications of the technique to antimicrobial evaluations, overnight fasted dental plaque is collected from a non-treated quadrant of the dentition along the gingival margin. Topical formulations are used in vivo. Following this, dental plaques are collected from other dentition quadrants at extended times, allowing for the back diffusion, clearance and natural intraoral deactivation of antimicrobials within the oral cavity. In vivo treated and non-treated plaque samples are subsequently tested for metabolic and regrowth activity under controlled and standardized conditions in vitro following normalization for biomass. The technique thus combines the necessary biological factors important to the legitimate evaluation of antimicrobial effects in vivo, while benefiting from the improved precision and control provided by in vitro assessment of plaque activity. In this paper evidence is presented validating the PGRM method, and initial activity screens of commercial antimicrobial mouthrinses and toothpastes, including a new stabilized stannous fluoride dentifrice, are described.