The aim of the present study was to evaluate the effect of natural deproteinized bone mineral on the temporal and spatial pattern of bone formation in a guided bone regeneration model system while using a bioresorbable membrane device. A periosteal skin flap was raised uncovering the calvaria of 20 rabbits. A stiff hemispherical dome made of polylactic acid was placed onto the roughened calvaria and anchored by screws. Prior to placement, the dome was either filled with peripheral blood (control group, 8 rabbits) or with blood and OsteoGraf/N-300 (test group, 12 rabbits). At 1 month, histologic sections revealed bone regeneration in both test and control domes to various degrees. In the test domes, bone height reached 78% (67-83) and bone volume was 11% (6-17), while in the control domes, bone height was 45% (14-67) and bone volume 6% (1-11). At 2 months, bone height was unchanged in the test group at 70% (67-83) and bone volume had only slightly increased to 16% (11-21). In the controls, height increased to 86% (60-100) and volume to 20% (9-27). Thus, in this model system, natural bone mineral fill contributed to accelerate initial bone neogenesis, while it did not contribute to increasing bone volume or bone height at later observation stages.