The contribution to bioactivity of F-addition to bioactive glasses seems not well resolved. In this work is reported the surface reactivity in different solutions (DMEM and TRIS) of some potentially bioactive glasses based on the composition of 45S5 bioactive glass, in which CaF2 substitutes alternatively (part of) CaO and Na2O, as compared to the reactivity of 45S5 bioactive glass. This study is aimed at explaining in some detail the mechanism and the rapidity of formation of an apatitic crystal phase at the interface between the inorganic material and simulated biological media.Using a multi-technique investigation approach, we propose a set of reactions, involving Ca-carbonates formation, that is somewhat different from that proposed by Hench for 45S5 bioactive glass, and occurs when a F-containing glass surface is contacted with a simulated body solution. The usefulness of IR spectroscopy in recognizing the starting step of apatite (fluoro-apatite) formation, with respect to XRD technique, is well established.