The aim of the present study was to compare the resistance of fluoroapatite (shark enamel) and hydroxyapatite (human enamel) against a high caries challenge in a human in vivo model. Two samples of shark enamel and human enamel were each placed in removable appliances in six children and carried for 1 month and a plaque retentive device was placed over each enamel sample. The results showed that the mean total mineral loss (delta Z) was 1680 vol% micron in human enamel and 965 vol% micron in shark enamel. The corresponding mean values for lesion depth were 90 micron and 36 micron, respectively. It is concluded that even shark enamel containing 30,000 ppm F has a limited resistance against caries attacks.