The presence of calcium-releasing ingredients in toothpastes containing sodium fluoride is usually avoided to prevent loss of active fluoride due to the formation of the insoluble calcium salt. The purpose of this study was to determine the bio-availability of fluoride from Enamelon Toothpaste (E), which simultaneously supplies fluoride, calcium and phosphate salts from a dual dispensing package. Fluoride uptake into artificially lesioned enamel cores due to the use of the test dentifrice (E) diluted 1:3 in whole human saliva was compared to that from a clinically proven effective sodium fluoride/silica USP reference toothpaste (C) and a non-fluoride control (E-w/o F). Enamel solubility reduction due to the use of E, C and E-w/o F was measured by determining the quantity of phosphate released to lactic acid buffer before and after treatment of the crowns of molars with 1:3 slurries of the dentifrices in water. Fluoride uptakes and enamel solubility reductions were 5031 +/- 158 ppm and 21.6 +/- 2.2% for E, 1915 +/- 39 ppm and 13.6 +/- 2.0% for C, and -3 +/- 2 ppm and 0.8 +/- 1.7% for E-w/o F. The fluoride uptake and enamel solubility reductions from E were significantly greater than from C (p < 0.001, Fisher LSD), and both fluoride-containing dentifrices significantly outperformed E-w/o F (p < 0.001). The laboratory results indicate that the calcium and phosphate salts delivered by the remineralizing Enamelon dentifrice increase the bioavailability of fluoride to substantially exceed that of the clinically proven standard dentifrice.