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Abstract Dental caries is one of the most prevalent and costly oral chronic infectious diseases worldwide . Anti‐caries agents inhibit the production of bacterial acid and modulating the demineralization-remineralization equilibrium of dental hard tissues. Fluoride is the most commonly used remineralizing agent. Fluoride can be delivered topically and systemically. However, fluoride application has its innate limitations like acute/chronic fluorosis at high doses. Topical application of high concentration fluoride may also seal the enamel surface before the remineralization of subsurface zone. Therefore, fluoride is far from a complete cure, and it is essential to have alternative and effective anti‐caries approaches. The caries lesion is reversible via a remineralization process involving the diffusion of minerals into the subsurface lesion to restore the lost tooth structure. Aim of the study: The aim of study is to evaluate and compare the effects of 2.5% concentration of arginine and 8% concentration of arginine on uptake of fluoride on demineralized enamel surfaces (in vitro) by measuring: 1- Surface micro-hardness using (vicker test). 2- Morphological alteration using Environmental scanning electron microscope (ESEM). 3- Mineral content using Energy dispersive x-ray spectroscopy (EDX). Summary 58 Materials and methods: Forty extracted premolars were collected from outpatient clinic of Maxillofacial department, Faculty of Dentistry, Suez Canal University. They were divided into four groups: group I (negative control group): (20demineralized specimens) were treated by artificial saliva and then divided into: Subgroup Ia: 10 specimens were subjected to surface microhardness measurements (SMH) (vicker test). Subgroup Ib: 10 specimens were examined for scanning electron microscope and then EDX analysis. group II: (positive control group): (20 demineralized specimens) were treated with sodium fluoride (NaF) solution (500ppmf) as remineralizing agent. Subgroup IIa: 10 specimens were subjected to surface microhardness measurements (SMH) (vicker test). Subgroup IIb: 10 specimens were examined for scanning electron microscope and then EDX analysis. group III: (20demineralized specimens) were treated by sodium fluoride solution (NaF500ppmf) + arginine solution (2.5%) as remineralizing agent. Subgroup IIIa: 10 specimens were subjected to surface microhardness measurements (SMH) (vicker test). Subgroup IIIb: 10 specimens were examined for scanning electron microscope and then EDX analysis. Summary 59 group IV: (20demineralized specimens) were treated with sodium fluoride solution (NaF 500ppmf) + arginine solution (8%) as remineralizing agent. Subgroup IVa: 10 enamel specimens were subjected to surface microhardness measurements (SMH) (vicker test). Subgroup IVb: 10 specimens were examined for scanning electron microscope and then EDX analysis Results: There was a statistically significant difference between microhardness values of the four groups; group III and group IV showed the highest microhardness value respectively followed be group II and finally the least value was recorded related to group I. The Scanning Electron micrograph of enamel of group I showed porous enamel surface, while in group II showed increase amount of opaque deposition on enamel surfaces. However both group III&IV showed evenly distributed opaque deposition on enamel surfaces of samples. There was No statistically significant difference between F value in comparison between group I, group II &group IV, while group III showed the statically significant high mean F value. There was No statistically .significant difference between Ca:P value of group I,II,III, and IV |