We studied nerve ingrowth into a cancellous bone graft in a bone conduction chamber model in the rat. Before implantation of the chamber bilaterally in the proximal tibiae of 8 Sprague-Dawley rats, a defatted cancellous bone graft from separate donor rats was fitted snugly into each chamber. After 6 weeks, the animals were perfused with Zamboni's fixative and the chambers were harvested. Immunohistochemical detection of nerve fibers was performed in cryostat sections, using antisera to protein gene product 9.5 (PGP 9.5), neural growth-associated protein GAP-43/B-50, calcitonin gene-related peptide (CGRP), substance P and C- flanking peptide of neuropeptide Y (CPON). Nerve fibers were found in 10 out of 16 samples in the newly formed bone, and also in the fibrous tissue which had penetrated deeper into the graft. The nerve fibers were mainly of sensory origin, as they showed immunoreactivity for CGRP and GAP-43/B-50. We speculate that the nerve fibers may act as transmitters of nociceptive impulses from the graft, and as transport pathways for neuropeptides that are actively involved in angiogenesis and in the recruitment and activity of osteogenic cell populations from the graft recipient.