A Plaque Glycolysis and Regrowth Method (PGRM) has been used to examine the effects of single brushing with a new stabilized stannous fluoride dentifrice on plaque acid production. Plaque samples collected 45 minutes after subject toothbrushing were compared with samples collected prior to toothbrushing for glycolytic activity (pH reduction in incubation media), and the composition and proportion of acids produced during metabolism (capillary electrophoresis). Subjects brushed with both active SnF2 and placebo dentifrices in a cross-over design. Acetic and lactic acid were found to be produced during PGRM metabolism. SnF2 dentifrice was observed to significantly inhibit plaque glycolysis, reducing the pH drop associated with acid production. and specifically inhibiting both lactic acid and acetic acid production. Control dentifrice had a modest inhibitory effect on acid production, primarily inhibiting acetic acid production. SnF2 dentifrice inhibited lactic acid production more effectively than control dentifrice, and this effect appeared to be related to SnF2 specificity in metabolic inhibition, as opposed to the components of control dentifrice, namely ionic fluoride and surfactant. These experimental results support the in vivo antimicrobial activity of SnF2 formulated in a new stabilized matrix (currently marketed as Crest Gum Care), and demonstrate the utility of the PGRM method in elucidating specific mechanisms of action for antimicrobial agents.