The response of bovine enamel to intra-oral cariogenic environments was studied in human volunteers. Enamel slabs were mounted in dentures and treated with either 10% sucrose or 10% sucrose plus 20 ppm fluoride mouthrinses for one minute five times daily. After one week, these enamel slabs were studied for change in surface hardness and for the degree of fluoride incorporation, or for their resistance to acid acquired by the intra-oral exposure. Among the eight subjects, those with the highest experimental cariogenicity exhibited the highest benefit of enamel from the fluoride in terms of fluoride incorporation and in their resistance to the subsequent acid test. The results suggest that cariogenic activity and fluoride will synergistically improve the tooth resistance to subsequent attack, apparently through mineral exchange that favors the formation of acid-resistant minerals with high fluoride content within enamel lesions.