The current study proposes a pH-cycling model to verify the dose-response relationship of fluoride-releasing materials in their ability to reduce in vitro demineralization. Sixty bovine enamel blocks (4 x 3 x 3 mm) were selected, using baseline surface microhardness (SMH1) evaluations at different distances from the enamel sectioned border (150, 300, 450 and 600 microm). Specimens (n=48) were prepared with Z100, Fluroshield and Vitremer at the standard powder/liquid ratio and at a 1/4 diluted-powder/liquid ratio. The 12 remaining specimens were used as a control group. The specimens were submitted to a pH-cycling model with high cariogenic challenge. After pH-cycling, final surface microhardness (SMH2) was assessed to calculate the percentage change of surface microhardness (%SMHc). Next, the fluoride present in enamel (microg F/mm3) and in pH-cycling solutions (microg F) was measured. Cross-sectional microhardness was done to calculate the mineral content (deltaZ). Data from %SMHc, deltaZ and microg F were analyzed by analysis of variance (p < 0.05), while microg F/mm3 analysis was done using the Kruskal-Wallis test. The results showed a correlation between %SMHc and microg F/mm3 (r3 = 0.4129; p < 0.0001), %SMHc and microg F (r2 = 0.4932; p < 0.0001), deltaZ and microg F/mm3 (r3 = 0.4573; p < 0.0001), micorg F/mm3 and microg F (r2 = 0.3029; p < 0.0001) and between deltaZ and microg F (r2 = 0.5276; p < 0.0001). The pH-cycling model allowed the in vitro verification of the dose-response relationship of fluoride-releasing materials in the demineralization of enamel.