Human tooth enamel exhibits a unique microstructure able to sustain repeated mechanical loading during dental function. Although notable advances have been made towards understanding the mechanical characteristics of enamel, challenges remain in the testing and interpretation of its mechanical properties. For example, enamel was often tested under dry conditions, significantly different from its native environment. In addition, constant load, rather than indentation depth, has been used when mapping the mechanical properties of enamel. In this work, tooth specimens are prepared under hydrated conditions and their stiffnesses are measured by depth control across the thickness of enamel. Crystal arrangement is postulated, among other factors, to be responsible for the size dependent indentation modulus of enamel. Supported by a simple structure model, effective crystal orientation angle is calculated and found to facilitate shear sliding in enamel under mechanical contact. In doing so, the stress build-up is eased and structural integrity is maintained. © 2014 Elsevier Ltd.