Dose-related remineralization of enamel lesions was studied in situ. Enamel specimens with subsurface lesions were mounted on lower molars bilaterally and exposed to five regimens: (A) control with a F-free dentifrice three times daily; (B) NaF dentifrice brushed three times daily; (C) fluoride-releasing device (FRD; 0.07 mg F/day release rate) plus F-free dentifrice; (D) FRD (0.232 mg F/day) plus F-free dentifrice, F/day and (E) FRD (0.232 mg/F/day) plus NaF dentifrice. Resting and stimulated saliva samples were obtained for salivary flow and F content determinations. Twenty-eight subjects participated in this double-blind, random-assignment crossover study. After 50 days the enamel specimens were recovered, sectioned, microradiographed, and scanned with image analysis. Regimens D and E demonstrated approximately 30% additional remineralization as compared with to controls, and regimens B and C showed 13.7 and 10.5% increased remineralization as compared with to controls. The increased remineralization of the regimens generally paralleled the increase in salivary F and clearly demonstrated a dose-related response which was some threefold in relation to release rate, salivary F, and percent remineralization.