The intra-oral cariogenicity test (ICT) in situ experimental model was introduced in 1964 for the study of caries on sample enamel in the human mouth. Slabs of human or bovine enamel are mounted with a Dacron gauze cover in the acrylic flanges of prosthetic appliances. The extent of enamel demineralization or remineralization of lesions is assessed from surface microhardness measurements and microradiography of the enamel sections. The ICT model offers the potential of studying various parameters related to caries. This publication presents a typical ICT study comparing the cariogenicity of 10% sucrose solutions containing 1, 3, 10, and 30 ppm F with that of the control solution, 10% sucrose (without fluoride). The treatments were applied to the ICT as 10-minute extra-oral immersions. The results indicate: (1) a strong effect of F in decreasing demineralization of sound enamel and increasing remineralization of pre-softened enamel in the ICT; (2) pronounced resistance to a subsequent in vitro acid test; (3) pronounced F incorporation into pre-softened enamel; and (4) a characteristic acid-resistant zone, as seen in microradiographs, associated with exposure to F. This in situ model enables one to study experimental caries with repeated testing of enamel that follows the development and/or the regression of subsurface enamel lesions, F incorporation, increased acid resistance, cariogenicity of substrates, and other parameters of caries that can be assessed under standard conditions of tooth substrate and microbial sheltering.