Objectives: Sex hormone receptors are reported to be present in human dental pulp (HDP) cells. The purpose of this study was to examine the biological significance of estrogen and androgen receptors (ER and AR, respectively) in HDP cells. Design: We isolated HDP cells expressing ER- and AR-mRNAs and investigated the expression status of the receptors and the response to sex hormones in the cells. Results: HDP cells expressing ER- and/or AR-mRNAs had the ability to form alizarin red S-positive nodules in which calcium and phosphorus were deposited in vitro and to differentiate into odontoblasts-like cells and dentin-like tissue in vivo. Individual clones isolated from HDP cells exhibited a different expression pattern of mRNA for ER and AR. Some clones expressed ERα- and/or ERβ-mRNAs and the others coexpressed ER- and AR-mRNAs. Using the Ingenuity software, we found that 17β-estradiol (E2) and dihydrotestosterone (DHT) could act directly on HDP cells through ER- or androgen signaling-mediated mechanisms. E2 or DHT stimulated the mRNA expression for genes related to odontogenesis of dentin-containing teeth and odontoblast differentiation, suggesting that ER and AR in HDP cells may be involved in dentinogenesis. Conclusions: Our findings provide new insights into the biological significance of sex hormone receptors in HDP cells. Gene expression profiles of human dental pulp cells derived from one male patient were compared between cells treated with 10^-6 M 5alpha-dihydrotestosterone and cells treated with vehicle. Each sample has one replicate. Gene expression profiles of human dental pulp cells derived from one female patient were compared between cells treated with 10^-9 M 17beta-estradiol and cells treated with vehicle. Each sample has one replicate.