The final aim of our study is to develop a novel calcium phosphate cement based on zinc-containing alpha-tricalcium phosphate (alpha ZnTCP) and evaluate its potential as bonegraft material in vivo. In the present study. in vivo efficacy of zinc in hardened bodies of alpha ZnTCP was explored. The hardened bodies prepared from alpha ZnTCP with zinc content of 0.00, 0.04, 0.08, 0.11 and 0.19 wt.% were prepared by mixing pure alpha TCP or alpha ZnTCP powder with 12 wt.% sodium succinate solution at a solid-to-liquid ratio of 2.0. Due to the release of zinc ions into the physiological salt solution during curing, the zinc content in the hardened bodies was calculated to be 0.00, 0.03, 0.06, 0.10 and 0.18 wt.%, respectively. The hardened bodies were implanted in the femora and tibia of white rabbits for 4 weeks. Histological and histomorphometric evaluation showed that the hardened body containing 0.03 wt.% zinc, significantly promoted more new bone formation without evoking adverse tissue reactions than that without zinc. The hardened bodies containing 0.06 and 0.10 wt.% zinc also resulted in the increase in numbers of active osteoblasts surrounding the new bone but caused inflammation at the implant sites. Results of this study indicate that the hardened body prepared with alpha ZnTCP is superior to that prepared with alpha TCP in promoting new bone formation due to the release of zinc ions. This study also indicates that the optimum amount of zinc in the hardened body is about 0.03 wt.% to avoid inflammatory reaction. (C) 2008 Elsevier B.V. All rights reserved.