The chemical reactions between hydroxylapatite (HA) and titanium were studied in three different kinds of experiments to increase understanding of how to bond HA to titanium for implant materials. HA powder was bonded to a titanium rod with hot isostatic pressing. Interdiffusion of the HA elements and titanium was found in concentration profiles measured in the electron microprobe. Titanium was vapor-deposited on sintered HA discs and heated in air; perovskite (CaTiO3) was found on the HA surface with Rutherford backscattering and X-ray diffraction measurements. Powder composites of HA and titanium and TiO2, were sintered at 1100degreesC; again, perovskite was a reaction product, as well as beta-Ca-3(PO4)(2), from decomposition of the HA. These results demonstrate chemical reactions and inter-diffusion between HA and TiO2 during sintering, resulting in chemical bonding between HA and titanium. Thus, cracks and weakness at HA-titanium interfaces probably result from mismatch between the coefficients of thermal expansion of these materials. HA composites with other ceramics and different alloys should lead to better thermal matching and better bonding at the interface. (C) 2003 Wiley Periodicals, Inc. J Biomed Mater Res 65A: 336-343, 2003.