Background: This study aimed to investigate the effect of silver and fluoride ions on demineralization of enamel. Methods: The coronal parts of 40 extracted sound premolars were prepared into tooth blocks. An unvarnished occlusal surface window (OW) and a flat buccal ⁄ lingual surface window (FW) were created for each tooth by covering all other surfaces with an acid-resistant varnish. These blocks were randomly allocated into four groups of 10 blocks each and immersed in respective solutions for 5 minutes: Group 1 -2.36 M silver fluoride; Group 2 -2.36 M potassium fluoride; Group 3 -2.36 M silver nitrate; and Group 4 -deionized water. After 7-day immersion in a buffered demineralization solution at pH 4.4, micro-CT scans were taken. Results: Mean lesion depth in the FW area for tooth blocks in AgF, KF, AgNO 3 and control groups were 0 lm, 3.3 ± 10.3 lm, 156.3 ± 30.8 lm, and 173.6 ± 48.6 lm, respectively (p < 0.001). The difference in mean lesion depth between the AgNO 3 and control groups was not statistically significant (p > 0.05). Similar OW and FW lesions were observed in tooth blocks in the AgNO 3 and control groups. Conclusions: Topical application of a 2.36 M fluoride solution can inhibit demineralization of enamel while topical application of silver ions has little effect.