The capacity of hydroxyapatite (HA) implants to support large defect repair in weight-bearing long bones of large size animals was investigated. Diaphyseal resections 3.5 cm of the tibia were performed in five adult sheep. They were substituted with HA macroporous ceramic cylinders anatomically shaped, and an external fixator was assembled. The sheep were sacrificed at 20, 40, 60, 120, and 270 days after surgery, respectively. Histology and micro X-ray study of resected implants and adjacent tissues showed proper integration of ceramic with newly formed periosteal bone as early as 20 days after surgery. In one sheep, the external fixator was removed 5 months after surgery. The animal gained the ability to walk with no functional impairment until it was sacrificed 4 months later. At this time, extensive integration of ceramic with bone was detected radiographically and confirmed by a morphological study of the resected sample. Our data indicate that large defects in a weight-bearing long bone can be repaired to the extent necessary for full functional recovery in large animals. These data set the stage for further intervention on material properties as well as for preliminary attempts to use ceramic prostheses for reconstruction of large bone defects in humans.