The proposed studies are designed to continue our exploration of the mechanisms by which fluoride is incorporated into developing enamel, especially as it is related to fluoride movement through the enamel organ and binding by the enamel matrix proteins. The work is a logical extension of findings generated during the previous and current project periods, and will further define the physiologic and potentially pathologic effects of fluoride on enamel formation. Our previous work indicates that there is a multi-compartment mechanism for the uptake of fluoride in developing enamel and that one or more of these compartments is readily reversible; that passage of fluoride through the enamel organ is diffusion controlled; and that the water space and fluoride uptake pattern in developing enamel are related. The proposed studies will test these corolaries of our general hypothesis. The proposed specific aims are: (1) to determine the changes in fluoride concentrations in secretory and maturing enamel and in bone in response to changes in plasma concentrations of fluoride; (2) to more completely define the fluoride binding and exchange characteristics of secretory and maturing enamel, enamel mineral, and enamel matrix; (3) to determine if the movement of fluoride into secretory and maturation stage enamel is diffusion controlled; (4) to determine if uptake of 18F in maturation stage enamel is influenced by the concentration of fluoride in the extracellular fluids; (5) to determine the water distribution in developing enamel and to examine the relationship between water distribution and fluoride uptake.