Characterization of lead substitution for calcium in hydroxyapatite (CaHA) is carried out, using experimental techniques and Density Functional theoretical (DFT) analyses. Theoretical modeling is used to obtain information of the Pb chemical environment for occupancy at either Ca(I) or Ca(II) sites of CaHA. Effects of the larger ionic radius of Pb(+2) compared to Ca(+2) are apparent in embedded cluster calculations of local chemical bonding properties. DFT periodic planewave pseudopotential studies are used to provide first-principles predictions of local structural relaxation and site preference for Pb(x)Ca(10-x)HA over the composition range x< or = 6. General characteristics of the polycrystalline material are verified by X-ray diffraction and FTIR analysis, showing the presence of a single phase of CaHA structure. A short range structure around lead is proposed in order to interpret the Pb L-edge EXAFS spectrum of the solid solution Ca(6.6)Pb(3.4)HA. In this concentration we observe that lead mainly occupies Ca(II) sites; the EXAFS fit slightly favors Pb clustering, while theory indicates the importance of Pb-Pb avoidance on site (II).