Our previous studies showed that synthetic octacalcium phosphate (OCP) enhances bone regeneration more than hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP). Also, a synthetic bone substitute constructed of synthetic octacalcium phosphate (OCP) and porcine atelocollagen sponge (OCP/Col) showed stable bone regeneration. The present study was designed to investigate the difference of bone regeneration by OCP/Col and other calcium phosphate-collagen composites. OCP/Col, β-TCP$-collagen% composite (β-TCP/Col), or HA$-collagen% composite (HA/Col) sponge was prepared from pepsin-digested atelocollagen isolated from the porcine dermis and OCP, β-TCP, or HA granules, respectively. A standardized critical-sized defect was made in the rat calvarium, and various calcium phosphate-collagen composites were implanted into the defect. The rats were fixed at four weeks after implantation and radiographic and histological examinations were performed by undecalcified cross sections of implants. Radiographic examination showed that uniform radiopaque masses were observed in the created defects treated with OCP/Col, whereas granulous and foggy radiopacity was observed in β-TCP/Col and HA/Col. Histological examination showed that newly formed bone was observed in the reticulum of OCP/Col and around the implanted OCP. The regenerated bone by β-TCP/Col or HA/Col seemed to be less than that by OCP/Col and would not to be nucleated by the granules of β-TCP or HA. The present study indicated that bone regeneration by OCP/Col was different from those of β-TCP/Col and HA/Col. Application of OCP/Col would be expected for clinical use in the future.