Acids produced by various oral bacteria cause mineral loss and crystallite dissolution during the development of enamel caries. In order to demonstrate this phenomenon, the initial disappearance of lattice fringes and the formation of a central perforation in crystallites were examined by high resolution electron microscopy (HREM) in initial enamel caries without macroscopic tissue evidence of destruction. Ultrathin sections were also examined by selected area electron diffraction to reveal the mineral phase of the surface layer in carious enamel. A marked variation in the dissolution pattern was disclosed in the initial carious lesions. HREM revealed that disappearance of the lattice fringes from the lateral portion of the crystallites was predominant in the superficial layer covering the lesion, while central perforation of crystallites mainly occurred in the subsurface prismatic region. The beginning of the central dissolution occurred at the dislocated area where lattice striations appeared to be disordered. Selected area electron diffraction of the gradually demineralized enamel revealed a pattern consistent with hydroxyapatite (OH-AP) or fluorapatite (F-AP) mineral. These findings suggest that the susceptibility to caries of enamel crystallites is spatially and temporally different during the progression of the caries. Furthermore, the formation of central perforations and the consequent easy intracrystalline diffusion of acids might induce rapid crystallite dissolution.