The purpose of this study was to investigate whether the lesion of incipient caries was associated with morphological differences between the molars of C3HJHeJ and C57BL/6J mice. The caries scores for C57BL/6J and C3HJHeJ at 35 days old were 3.8±2.5 and O±O (mean±SD), respectively. The caries scores for C57BL/6J and C3H/HeJ at 49 days old were 42.4±8.3 and 4.2±2.4 (mean±SD), respectively. There was a 10-fold difference between C57BL/6J and C3HJHeJ in terms of caries progress. Incipient caries then appeared at the second fissure of lower MI. The central region of the second fissure of lower Ml in C57BL/6J was deeper and rougher than the same region in C3HJHeJ. The Ca/P ratios of the fissure for C57BL/6J and C3HJHeJ were 1.69±O.27 and 1.71 ±0.25 (mean±SD), respectively. The total data showed no significant difference between C57BL/6J and C3HJHeJ.In conclusion, it was found that incipient caries appeared at the second fissure of lower MI. Moreover, it is suggested that the morphology of the fissure as well as the immune responses may be responsible for the dental caries caused by stagnation of bacterial plaque.