In human periosteum-derived osteoblastic cells (SaM-1) and human osteosarcoma-derived cells (SaOS-2, HOS, MG-63), the mRNA expressions of calcitonin gene-related peptide receptor (CGRP-R), substance P receptor (SP-R), neuropeptide Y receptor (NPY-R), beta-adrenergic receptors (beta1-R, beta2-R, beta3-R), vasoactive intestinal polypeptide type 1 and type 2 receptors (VIP-1R, VIP-2R) and pituitary adenylate cyclase activating polypeptide receptor (PACAP-R) were examined by reverse transcription-polymerase chain reaction (RT-PCR). According to the magnitude of the mRNA expression of alkaline phosphatase (ALP), the relative state of commitment of these osteoblastic cell lines to the osteoblast lineage was SaM-1 > SaOS-2 > HOS > MG-63. CGRP-R, NPY-R, VIP-1R and beta2-R, but not SP-R, VIP-2R, PACAP-R, beta1-R and beta3-R, were expressed in osteoblasts as well as osteosarcoma cells. Expression of these receptors seems to be a common feature in osteoblastic cells, but the magnitude of expression was not dependent upon the relative state of commitment of the osteoblastic cells to the osteoblast lineage. In addition, VIP mRNA was not expressed in osteoblastic cells, suggesting the absence of an autocrine system of VIP in osteoblasts. These observations suggest that these neuropeptides and norepinephrine are involved in local regulation of human bone metabolism.