In this study, we describe the distribution of fibres that contain calcitonin gene-related peptide in normal bones and in bones that are remodeling after insertion of an implant. With routine histology and antibodies to calcitonin gene-related peptide, small neural and free-running fibres staining positively for calcitonin gene-related peptide were found in the periosteum, endosteum, and cortical bone of the tibia in the goat. In many cases, the free-running fibres were associated with blood vessels that entered the bone through Volkmann's canals. The endosteal blood supply was destroyed as a result of insertion of the implant. The necrotic bone was no longer innervated, as shown by the lack of staining for the antibodies. At 6 weeks, a repair phase started with revascularization and remodeling of the necrotic endosteal bone. During this repair phase, there was increased innervation with fibres containing calcitonin gene-related peptide in the remodeling cavities at the interface between living and necrotic bone. These fibres ended blindly, with many large varicosities, and could be demonstrated by immunostaining with monoclonal antibodies to B-50/growth associated protein-43, an antibody to outgrowing neuronal fibres. The correlative occurrence between extensive sprouting of fibres containing calcitonin gene-related peptide and the remodeling of necrotic endosteal bone suggests that sensory fibres with calcitonin gene-related peptide have a regulatory role in the control of angiogenesis or of bone remodeling associated with the insertion of an implant, or with both processes.