This in-vitro study evaluated the inhibition of demineralization in enamel sections produced by MI paste, fluoride and a combination of both, compared to artificial saliva and NaF 5000 ppm in a caries progression pH-cycling model. Twenty-one teeth were demineralized to create subsurface enamel lesions (approximately 200 microns in depth). The teeth were sectioned and characterized using polarized-light-microscopy (PLM). A single section from each lesion was assigned to a treatment group: Artificial saliva, NaF 5000 ppm (Prevident, Colgate), MI paste (Recaldent, GC America Inc), NaF 1100 ppm (Crest, Procter & Gamble) and NaF 1100 ppm plus MI paste. The sections were covered with varnish except for an exposed window on the external surface of the lesion and placed in a six-day pH-cycling model with two daily treatment applications of two minutes each. The sections were characterized by PLM, and the lesion areas were measured using a digital image analysis system. Based on a paired-sample t-test, significant differences (p < .05) in percentage of change in lesion size were found between the high fluoride group and all the other groups. No significant difference was found between the artificial saliva and MI paste group, neither was there any significant difference between the NaF 1100 ppm, the combined application group or the MI paste group alone. In conclusion, the higher concentration of NaF (5000 ppm) reduced lesion progression to the greatest extent. The MI paste group did not show any effect on the inhibition of lesion progression. Further studies on the preventive effect and longer treatment applications are recommended.