Naturally occurring hydroxyapatite, Ca-5(PO4)(3)(OH) (HAP), is the main inorganic component of bone matrix, with synthetic analogues finding applications in bioceramics and catalysis. An interesting and valuable property of both natural and synthetic HAP is the ability to undergo cationic and anionic substitution. The lanthanides are well-suited for substitution for the Ca2+ sites within HAP, because of their similarities in ionic radii, donor atom requirements, and coordination geometries. We have used isothermal titration calorimetry (ITC) to investigate the thermodynamics of ion exchange in HAP with a representative series of lanthanide ions, La3+, Sm3+, Gd3+, Ho3+, Yb3+ and Lu3+, reporting the association constant (K-a), ion-exchange thermodynamic parameters (Delta H, Delta S, Delta G), and binding stoichiometry (n). We also probe the nature of the La3+:HAP interaction by solid-state nuclear magnetic resonance (P-31 NMR), X-ray diffraction (XRD), and inductively coupled plasmaoptical emission spectroscopy (ICP-OES), in support of the ITC results.