The purpose of this investigator-blinded, five-treatment, crossover human intraoral study was to evaluate the effects of two experimental dentifrice formulations containing either stannous fluoride (SnF2) or sodium fluoride (NaF) packaged with sodium hexametaphosphate in a dual-phase delivery system on demineralization-remineralization using an in situ model system. The experimental dentifrice formulations’ ability to alter demineralization-remineralization was compared to a series of three controls: SnF2-positive control, NaF-positive control and no-fluoride placebo-negative control. The single-section crown model, developed at the University of Iowa, was used to assess the fluoride efficacy of two experimental products versus the placebo containing no fluoride and positive controls. The results of the current in situ study suggest a clinical level of anticaries activity for the experimental SnF2 and NaF dentifrice formulations that was as good as either of the positive controls, when evaluated using polarized light microscopy. This supports the conclusion that the use of the sodium hexametaphosphate ingredient does not interfere with the normal fluoride activity of these toothpastes. In addition, the experimental SnF2 product was numerically better than both the NaF and placebo controls at preventing demineralization of sound root surfaces.