Experimentation in vitro using organic acid buffers as demineralizing media shows that caries-like lesions can be obtained which are very similar in morphology and developmental stages to early lesions formed naturally under oral conditions. The use of these chemical systems and of mechanistic models advanced to explain the unique histological features of incipient caries have yielded a good understanding of the processes involved in caries formation. The study of natural and induced factors influencing the demineralization process has been greatly facilitated by the use of bacteriological systems in which demineralization is produced by direct colonization of cariogenic microorganisms on the surfaces of extracted teeth. Comparison of results obtained with these latter systems and with chemical systems has allowed us, for example, to elucidate the mechanism by which acquired salivary pellicles and fluoride topical solutions decrease the rate of enamel demineralization. The pellicle retards transport of matter across the enamel surface, whereas the fluoride topical solutions decrease the cariogenicity of the colonizing bacteria.