This paper described an investigation of local resistance acquired in response to cariogenic attacks and remineralization periods from environmental fluids. Surfaces from extracted human teeth with yellow and brown areas indicative of consolidated carious lesions were exposed to acid buffers. Subsurface lesions were developed on areas of sound enamel adjacent to, but not in areas of, consolidated lesions. The development of higher tooth resistance to acid through demineralization and remineralization was demonstrated experimentally on bovine enamel presoftened in acid, treated with fluoride, exposed to the oral environment, and finally exposed to acid buffers for development of subsurface lesions. These results are interpreted as an extension of theory of tissue adaptation to an injurious challenge, in that the tooth surface is primed by the challenge for possible remineralization and the development of higher resistance. This, cariogenic challenges can result in either local adaptation of the enamel to the challenge through lesion consolidation or to open cavitation. As in any biological adaptation, the determining factors for the final outcome are: (a) the frequency and duration of the challenge, (b) the frequency and duration of remineralizing conditions, and (c) the composition of the remineralizing fluid. The implications of the theory in the pathogenesis of caries are discussed in the light of clinical and laboratory investigations.