Several biological materials have been analyzed in combination with osteo-inductive growths factors to determine whether such a system can replace bone grafting in surgical practice. Efforts have been aimed at the discovery of the best carriers and delivery systems. We present the results of the surgical treatment of 11 cranio-maxillo-facial defects in 9 patients using a combination of natural coral skeleton (NCS in blocks or granules), human fibrin glue and transforming growth factor beta-1 (TGF-beta 1) as a composite bone substitute. Three patients were initially excluded because of early extrusion of the materials due to a technical error. Clinical and radiological evaluation was performed in all cases, with the patient acting as his own control. Clinical firmness and radiological mineralization occurred in three quarters of cases. New bone formation was confirmed histologically in two of these patients. Clinically the initial results remained stable over a three years follow-up with staged surgical procedures performed on a number of patients. None of the patients suffered any detrimental effect from implantation of the bone substitute. Although the numbers in these series are limited, the association of TGF-beta 1, human fibrin glue and NCS represented an interesting step, although the clinical results could be improved. Important factors in the success of this technique appeared to be stabilisation of the biological materials, quality and asepsis of the surrounding tissue and the dose of growth factor.