ABSTRACT Objectives. To test whether the modified in-vitro pH-cycling model would work successfully as a means of investigating the de-/re-mineralization effects of nanoparticle hydroxyapatite toothpaste, and to compare such effects with those of sodium fluoride toothpaste. Methods. Sound extracted molars were painted, leaving a 1-mm wide window, and placed in a demineralizing solution for 96 hours to produce 100 to 120 孍 deep artificial carious lesions. The teeth were sectioned longitudinally (100 to 150 孍 thick) and divided into three groups (n=10 in each). Group A specimens were treated with a non-fluoride toothpaste containing 10% hydroxyapatite; group B (negative control) specimens were treated with a non-fluoride toothpaste containing 0% hydroxyapatite; while group C (positive control) specimens were treated with a fluoride (950 ppm sodium fluoride) toothpaste with 0% hydroxyapatite. The pH-cycling model was utilized for a period of 10 days. Results. For groups A and C, the mean depth (P<0.01) and the mineral content (P<0.05) of the lesions after treatment decreased significantly compared with baseline (paired t test), while the corresponding values for group B were significantly higher (P<0.001, paired t test). Furthermore, the maximum mineral content of the surface zone decreased significantly in group B but not in groups A and C. Conclusions. The modified in-vitro pH-cycling model successfully revealed progression and mineral changes in initial enamel lesions. Application of both the 10% hydroxyapatite and the 950 ppm sodium fluoride toothpastes reduced the rate of lesion progression when compared with application of toothpaste without either active ingredient.