The mineralized tissues are comprised from an ordered organic matrix, principally collagen fibers in bone and dentin, in which mineral crystals are deposited. There is a clear relationship between the structure of the matrix and the pattern of deposition of the mineral. The organic matrix components are laid down first, as the initial stage of normal bone and dentin calcification. The objective of our program is to understand the factors, at the molecular mechanistic level, which lead to this orderly deposition of mineral within the matrix. It appears that non-collagenous components of the matrix, phosphophoryns in dentin, interact with collagen at the mineralization front. Because of their high calcium ion affinity, the phosphophoryns, we postulate, fix the first layer of calcium ions upon which further crystal growth can occur. Present studies deal with: 1) the properties of the phosphophoryns; 2) the biosynthesis and secretory pathway of the phosphophoryn; 3) the nature of the interaction between phosphophoryn and collagen at the mineralization front, and 4) the nature of the analogous phosphophoryns (or other acidic proteins) in bone.