The caries inhibitory effect of topical applications of 200 ppm fluoride from neutral sodium and ammonium fluoride solutions was tested in the hamster. Similarly, 1,000 ppm fluoride from sodium and ammonium fluoride solutions with and without orthophosphate at pH 5 and 7 was tested in the rat. Also tested in the hamster study was the combination of neutral sodium or ammonium fluoride with Zonyl FSC (DuPont de Nemours, Wilmington, Del., USA). This positively charged surfactant accelerates the formation of apatitically bound fluoride during fluoride enamel interactions. Findings in the hamster study show that repeated fluoride treatments (4 per week) depressed caries in (M1 + M2), but not in M3. Considering individual groups, only the animals treated with the sodium fluoride with Zonyl FSC experienced significantly less caries than the control group (M1 + M2). The findings in the rat showed all the fluoride-treated animals to experience less caries than the control group. Although the greatest caries inhibition resulted from repeated applications of ammonium fluoride with phosphate at pH 5, there was no statistically significant superiority of ammonium fluoride over sodium fluoride, irrespective of the presence of orthophosphate. On the other hand, solutions with orthophosphate were more effective than those without at pH 5, irrespective of whether the cation was sodium or ammonium. Finally, in the presence of orthophosphate, the sodium and ammonium fluoride solutions were more effective at pH 5 than at pH 7. A hypothesis is proposed explaining the differences in reactivity between NH4- and Na-fluoride solutions with enamel on the basis of the structure of the solutions and access of the ions to the solid-liquid interface.