OBJECTIVE The aim of this in vitro study was to assess the effect of toothpastes containing three different sodium fluoride concentrations and a calcium sodium phosphosilicate system, on root dentine demineralization and remineralization. METHODS During a fourteen-day pH-cycling protocol, pre-softened bovine root dentine specimens were immersed twice daily, before and after the demineralization periods, for 2 min, in the following toothpaste slurries: (a) non-fluoridated (control), (b) 7.5% calcium sodium phosphosilicate, (c) 1450 ppm F, (d) 2800 ppm F, and (e) 5000 ppm F. Subsequently, the slabs were subjected to a fifty-hour acid resistance test. Knoop microhardness at different lesion depths was assessed in specimen cross-sections and KHN values were converted to vol.% mineral. Comparisons between the groups were performed at each lesion depth through ANOVA-based tests and furthermore, regression analysis of the derived statistic of "integrated vol.% mineral loss" was carried out. Also, lesions were evaluated qualitatively using transmission and polarized light microscopy. RESULTS The 5000 ppm F toothpaste group, during pH-cycling, presented significantly less total vol.% mineral loss and subsequently exhibited considerably increased surface acid resistance, compared to all the other tested groups. The calcium sodium phosphosilicate toothpaste, during pH-cycling, inhibited demineralization and/or promoted remineralization of the surface layers significantly more effectively than the control group nevertheless, subsequently, the acid resistance of the calcium sodium phosphosilicate dentifrice group was similar to that of the control group. These observations were confirmed by microscopic examination of the lesions. CONCLUSIONS Under the present experimental conditions, the 5000ppm F toothpaste, promoted remineralization and inhibited demineralization more effectively, than the other tested toothpastes.