INTRODUCTION: Investigators have been searching for alternative remineralizing compounds that have superior properties to those conventionally used; in order to reduce the risk of fluorosis in children. OBJECTIVES: To evaluate the anti-caries effect of hexametaphosphate (HMP) combined with low-fluoride toothpaste on primary teeth enamel surface using fluoride uptake analysis. MATERIALS AND METHODS: Seventy five freshly extracted anterior primary teeth were sectioned into two halves in a labiolingual direction (150 specimens). One half of each tooth remained untreated and served as control and the other corresponding half that was treated with the remineralizing toothpaste served as test. Specimens were assigned into subgroup IA (untreated) n=25, subgroup IB (250ppm F + 0.5% HMP) n=25, subgroup IIA (untreated) n=25, subgroup IIB (500 ppm F) n=25 and subgroup IIIA (untreated) n=25, subgroup IIIB (1000 ppm F) n=25. Specimens were subjected to pH cycling for five days and immersed in remineralizing solution for an additional two days. The enamel fluoride uptake analysis of specimens was evaluated quantitatively using an ion specific electrode. Data were analyzed using Mann-Whitney U, Kruskal-Wallis and Post-hoc pair-wise test. RESULTS: There was a significant high median enamel fluoride uptake between test subgroups IB (250ppm F + 0.5% HMP), IIIB (1000 ppm F) and their controls where p=0.008 and p=0.008 respectively, while there was no significant difference in median enamel fluoride uptake between the test subgroup IIB (500 ppm F) and its control subgroup IIA where p=0.690. Pairwise comparison of enamel fluoride uptake in the three test subgroups IB, IIB and IIIB showed significant high median value of subgroup IB than subgroup IIIB where p=0.027. CONCLUSIONS: A toothpaste containing 250ppm F + 0.5% HMP has a high anti-caries potential in comparison to pediatric 500 ppm F and standard 1000 ppm F toothpastes on primary teeth.