The aim of this work was preparation, characterization and bioactivity evaluation of nanocrystalline fluoridated hydroxyapatite (FHA) with different degree of fluoridation via the mechanical alloying (MA) method, and investigating the effect of MA parameters on the synthesizing process. Nanocrystalline FHA with a chemical composition of Ca-10(PO4)(6)OH2-xFx (where x values were selected equal to 0.0, 0.5. 1.0, 1.5 and 2.0) were synthesized using different milling conditions. X-ray diffraction (XRD), Fourier transform infrared (FTIR). transmission electron microscopy (TEM), scanning electron microscopy (SEM) and ICP-OES analysis techniques were utilized to characterize the synthesized FHA. In vitro tests were performed by immersing the prepared FHA in simulated body fluid (SBF). The changes of pH of the SBF were measured at pre-determined time intervals using a pH meter. The calcium and phosphorous ion concentrations of SBF were determined using the ICP-OES analysis. Bone-like apatite formation on the surface of the immersed samples was investigated by SEM. The results showed that only the FHA nanopowders, which were synthesized after 6 h of high-energy ball milling under optimized MA parameters including: 300 rpm of rotation speed, ball-to-powder weight ratio (B/P) equal to 35, and 8 balls with 20 mm in diameter, could fulfill the requirements of ASTM F1185-88 to be used as a biomaterial. In vitro test indicated that the dissolution rate of FHA decreased as the result of increasing the fluorine content of nanocrystalline FHA. Larger quantity of tiny nucleus was observed on the surface of samples with higher fluorine content after 8 h of soaking in the SBF. (C) 2008 Elsevier B.V. All rights reserved.