After an initial assessment of the experimental approach this experimental project was undertaken to study the regenerative response and incorporation of various implanted materials in calvarial bone defects in rabbits. Four 5-mm full-thickness defects were trephined in the frontal and parietal bones of the rabbits. After removal of the circular bone plugs the defects were used as recipient sites for inlay bone tissue and bone substitutes. In five separate studies the impact of bone regeneration of autogeneic bone grafts or eight bone substitutes were evaluated mainly by contact radiography, light microscopy and morphometry. The observation periods were four and 15 weeks. The main findings were: Autogeneic bone chips offered only minor advantages over controls in the model used and, also, differences in bone regeneration between diversified amounts of bone chips were negligible. In contrast, after bone paste implantation a cellular and mature bone was rapidly produced. Natural bone mineral (Bio-Oss) and synthetic dense hydroxylapatite ceramic proved to be biocompatible and a definite long term bone regeneration around all implants regardless of granulae size or resorbability was observed. Initial bone regeneration in and around the Bio-Oss particles was more extensive. Demineralized bone matrix of membranous and enchondral origins displayed extensive osteoinductive capacity and early bone production significantly exceeded that of control groups. The embryonic origin implied minor effects on the initial regenerative response only. Lyophilized bone allografts of two embryonic origins showed a low osteoinductive potential and a similar fashion of bone regeneration. No marked difference between these groups were displayed. HTR-polymer alone or combined with membraneous mineralized autogeneic bone chips showed a more rapid early bone regeneration than the groups containing lactomer beads, resorbable gel and controls. Also, the HTR-material proved to be a well-tolerated implant material by the recipient tissue bed.