The relationship between the amount of fluoride acquired by human enamel after varnish application and the resulting inhibition demineralization of is presented and discussed. Intact human enamel was pretreated with Fluor Protector varnishes with differing fluoride contents (0.7; 0.1; 0.05 and 0 wt% F-) for 24 hours. In a first experiment the amount of fluoride acquired after application was determined. In a second experiment the pretreated enamel was stored intra-orally under constant plaque coverage, in order to create a substantial demineralization challenge. The protection against demineralization, induced by the various varnishes was determined four months after varnish application using microradiography. Under the cariogenic conditions created in this study, the fluoride containing varnishes induced a protection of 53-75%. Although the amount of fluoride uptake was strongly related to the fluoride content in the varnishes, no statistically significant difference in demineralization inhibition between the varnishes was observed. SEM investigation of the enamel lesions revealed globular precipitates inside the fluoridated enamel, presumably consisting of calcium fluoride-like material. The present study indicates that the fluoride content in Fluor Protector varnishes can be decreased without reducing its ability to inhibit demineralization.