Neurogenic inflammation describes the local release of neuropeptides, notably substance P (SP), from afferent neurons and might play a role in the pathogenesis of pulpal disease. The fibroblast is the most numerous cell type in the dental pulp, and recent work has suggested that it is involved in the inflammatory response. Primary pulp fibroblast cell populations were isolated by enzymatic digestion. Whole pulp tissue was obtained from freshly extracted sound (n = 35) and carious (n = 39) teeth. Expression of SP and neurokinin-1 receptor (NK-1) mRNA by pulp fibroblasts was determined by reverse transcriptase polymerase chain reaction (RT-PCR). SP was expressed by pulpal fibroblasts at both mRNA and protein levels. In addition, NK-1 mRNA and protein expression was detected in fibroblast cultures by RT-PCR and Western blotting, respectively. SP levels, determined by radioimmunoassay, were significantly greater (P < .05) in carious compared with sound teeth. These findings suggest that pulp fibroblasts play a role in neurogenic inflammation in pulpal disease.