This investigation comprised two studies evaluating the effects of an acidic calcium phosphate solution (CPS) on fluoride uptake in the enamel, glycolysis of dental plaque, the incidence of dental caries and urinary fluoride concentrations of rats wearing an intraoral fluoride-releasing device (IFRD). In the first study, CPS-fluoride treatment preceded the cariogenic challenge. In the second study, the cariogenic challenge preceded the treatments. In the first study, CPS treatments increased the ability of enamel to bind fluoride. However, the enamel-bound fluoride exerted a negligible effect on plaque glycolysis as measured by the pH decrease after sucrose challenge. In the second study CPS augmented the caries inhibition for both the sulcal-morsal and buccal-lingual surfaces. In both studies the IFRD significantly restricted the development of carious enamel on the sulcal-morsal surfaces and caused elevated concentrations of fluoride in the urine independent of CPS treatments.