The effect of the neuropeptides substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) on DNA synthesis of dental pulp cells was investigated in cells grown from molar tooth bud explants from 4-6 days old rat pups. A concentration response-assay of Be proliferative response of pulpal cells was performed with SP, NPY, NKA, CGRP and VIP (0.01. to 1 nM) in the presence of EGF (10 ng/ml), hydrocortisone (0.4 mu g/ml) and 3% FCS, using [H-3]thymidine incorporation. The results showed that SP, NKA and CGRP, but not NPY and VIP, increased the cell number in a concentration-dependent manner, with maxima at 10(-10)-10(-9) M (SP, NKA) and 10(-7) M (CGRP), No potentiating effect was noted when cells were simultaneously stimulated with SP and CGRP. The finding that SP, NKA and CGRP have growth regulatory properties on pulpal cells in vitro suggests that sensory neuropeptides may be involved during pulpal development or in wound healing after pulpal injury.