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This study compared the cariostatic effect of a two-part, fluoride-calcium-phosphate-containing prototype dentifrice (containing 1100 ppm F) to a conventional, clinically proven effective "gold standard" (1100 ppm F, USP Standard) and an Enamelon placebo dentifrice (0 ppm F) using a rat model. Three groups of 18 Crl:CDR(SD)BR rats were inoculated with S. sobrinus 27352 and fed MIT-200 for 35 days in a programmed feeder. Double-deionized water (DDW) was given ad libitum. The rats were treated twice daily with one two-part dentifrice. Just prior to treatment, each of the two parts of dentifrice were mixed 1:1 and applied undiluted. The rats were euthanized and their mandibular molars scored for caries using the Keyes quantification method. Shrestha SNP caries scores were then calculated. Non-parametric comparisons were done among treatments at the 0.05 level of significance using analyses based on ranks. The mean Shrestha SNP Caries Scores +/- standard deviations for the prototype dentifrice, USP standard and Enamelon placebo were 84.9 +/- 62.8, 101.3 +/- 66.3, and 181.2 +/- 100.1, respectively. Scores for the 1100 ppm F prototype treatment were significantly lower than the USP Standard and the Enamelon placebo. These results indicate that the new prototype dentifrice, containing fluoride-calcium-phosphate, increased the anti-caries efficacy in a rat model when compared with a fluoride-containing USP Standard dentifrice.