In vitro studies suggest that enamel matrix derivative (EMD) affects the early stages of osteogenic maturation by stimulating bone cell proliferation. In the present study, we evaluated the effects of EMD and β-tricalcium phosphate (β-TCP) on bone augmentation within a titanium cap in rabbit calvaria, using 14 adult male Japanese white rabbits. The calvarium was exposed, a circular groove prepared, the marrow penetrated, and a standard hemispherical titanium cap placed in the groove. The cap was filled with a mixture of β-TCP and EMD at the experimental site, and was filled with β-TCP alone at the control site. At 1 and 3 months after cap implantation, animals were euthanized, and histological sections prepared. The sections were stained with basic fuchsin and methylene blue, and were examined using light microscopy. At 1 month, EMD tended to increase the amount of bone, but there was no significant difference in the amount of new tissue and mineralized bone between the experimental and control sites. The present findings indicate that the present mixture of EMD and β-TCP does not accelerate bone formation, compared with β-TCP alone. (J. Oral Sci. 47, 209-217, 2005)