Carbonate apatite (CO(3)Ap) blocks have attracted considerable attention as an artificial bone substitute material because CO(3)Ap is a component of and shares properties with bone, including high osteoconductivity and replacement by bone similar to autografts. In this study, we fabricated an interconnected porous CO(3)Ap block using alpha-tricalcium phosphate (TCP) spheres and evaluated the tissue response to this material in a rabbit tibial bone defect model. Interconnected porous alpha-TCP, the precursor of interconnected porous CO(3)Ap, could not be fabricated directly by sintering alpha-TCP spheres. It was therefore made via a setting reaction with alpha-TCP spheres, yielding interconnected porous calcium-deficient hydroxyapatite that was subjected to heat treatment. Immersing the interconnected porous alpha-TCP in Na-CO3-PO4 solution produced CO(3)Ap, which retained the interconnected porous structure after the dissolution-precipitation reaction. The diametral tensile strength and porosity of the porous CO(3)Ap were 1.8 +/- 0.4 MPa and 55% +/- 3.2%, respectively. Both porous and dense (control) CO(3)Ap showed excellent tissue response and good osteoconductivity. At 4 weeks after surgery, approximately 15% +/- 4.9% of the tibial bone defect was filled with new bone when reconstruction was performed using porous CO(3)Ap; this amount was five times greater than that obtained with dense CO(3)Ap. At 12 weeks after surgery, for porous CO(3)Ap, approximately 47% of the defect was filled with new bone as compared to 16% for dense CO(3)Ap. Thus, the interconnected porous CO(3)Ap block is a promising artificial bone substitute material for the treatment of bone defects caused by large fractures or bone tumor resection. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 269-277, 2019.