Prompted by severe problems in autogeneic and allogeneic bone transplantation, intensive efforts were made to find sufficient substitutes. A main demand on these materials, especially in healing of osseous defects, is to achieve results comparable to those of auto- or allografts. These must be related to their biomechanical and particularly to their biological properties, i. e. the ability to form new bone, osseous integration and physiological remodeling. Within different trials in the tibiae of sheep we investigated bone substitutes like hydroxyapatite ceramics (HA) or partially demineralized bone matrix (pDBM) and compared them to the gold standards of autogeneic and allogeneic bone transplantation. Therefore we used two different models: the drill hole model with small size defects of 6 mm in diameter and the shaft defect model as a true-to-life defect with a 5 cm large diaphyseal defect. Evaluation was done by X-rays, histology, microradioraphy, fluorescent microscopy and morphometry of the small size defects. HA showed only small effects on new bone formation and works merely as an osteoconductor. However, excellent new bone formation was regularly achieved by pDBM in the small defects, whereas it was limited in the large size defects. But considering their mechanism of action, it is possible to bridge large bone defects by pDBM.