Expression of retinoic acid receptor-beta (RAR-beta) is frequently lost in tobacco-related cancers. Benzo[a]pyrene diol epoxide (BPDE) is an active metabolite of tobacco procarcinogen benzo[a]pyrene and plays an important role in tobacco carcinogenesis. We therefore exposed SV-40 immortalized esophageal epithelial cells and esophageal cancer cells to BPDE to understand possible interactions between BPDE and RAR-beta expression. Our data showed that BPDE decreased RAR-beta mRNA surd protein levels by suppression of transcription of RAR-beta. Retinoic acid was able to partially block the inhibitory effect of BPDE on RAR-beta expression and to increase G1 phase of cell cycles. Furthermore, induction of COX-2 expression by BPDE was associated with RAR-beta inhibition. This study suggests that one way by which BPDE causes esophageal carcinogenesis may be through the inhibition of RAR-beta.