The inhibition of enamel demineralisation and the enhancement of remineralisation are positively but not linearly related to the concentration of fluoride, especially when high fluoride concentrations are used. The aim of this in situ experiment was to determine the maximum amount of enamel remineralisation that can be achieved with daily applications of very high concentrations of fluoride. For this purpose we compared the efficacy of a daily application of fluoridated topical gel (12,500 ppm F, partly as NaF, Olafluor and Dectafluor, pH 4.5) in combination with a fluoridated toothpaste (1,450 ppm F as NaF), with fluoridated toothpaste alone. Participants (n = 26, with partial dentures) were fitted with a demineralised enamel specimen (mean mineral loss of 1,674 vol%·μm) and were instructed to use one of the two fluoride treatments. After 4 weeks of treatment, the specimens were retrieved, a section was cut and analysed with microradiography. The remainder of each of the specimens was used for analysis of the 'loosely bound' and 'bound' fluoride. Fluoride was measured with gas-liquid chromatography. After 4 weeks in the mouth, the original lesion was reduced in size by 54% in the toothpaste + gel group (n = 14) and by 44% in the toothpaste-only group (n = 12), but the difference between the groups was not statistically significant. The mineral content profiles showed remineralisation of the lesions throughout the depth of the lesion. The enhancement of remineralisation by the high amounts of fluoride was most pronounced in the surface layer. For both the 'loosely bound' and 'bound' fluoride, a statistically significant increase in fluoride concentration could be found in the toothpaste + gel group. In the 4-week in situ period the use of high amounts of fluoride resulted in a maximum remineralisation rate. This is illustrated by an increase in remineralisation and higher fluoride concentrations in the toothpaste + gel group compared to the toothpaste-only group.