Bone and dentin consist of hydroxyapatite, collagen and body fluid. From biological points of view, we have been focusing on HAp and collagen materials for bone regeneration. The aim of this study is to estimate the appearance of multinuclear giant cells for non-organic (functionally graded HAp: fg-HAp) and organic materials (demineralized dentin matrix: DDM), histologically. The fg-HAp ceramic: Biomimetic fg-HAp was designed by using the partial dissolution-precipitation methods. The fg-HAp with micro-pores of 10-160 nm had larger specific surface areas (30-40 m2･g-1) than the synthetic HAp. Acid- insoluble dentin matrix (DDM): Human teeth were crushed under the cooling, completely demineralized in 0.026N HNO3 solution, and dried. The materials were implanted into the subcutaneous tissues (Wistar rats, 4 week-old, male), and removed at 1 and 4 weeks after the operations. Multinucleated giant cells were counted in the H-E sections. Giant cells predominantly appeared on the biodegradable micro-crystals at 1 week. The number of giant cells was more numerous in fg-HAp than in DDM. There was a significant difference in the cell number between fg-HAp and DDM. The absorption mechanism of fg-HAp should be predominantly cellular phagocytosis, while that of DDM might be predominantly enzymatic digestion. These data support the hypothesis that the biological HAp crystals may function as mineral signal in the recruitment and differentiation of multinucleated giant cells.