Dysregulation of G1 cyclins has been implicated in several human malignancies. To further investigate the role of G1 cyclins in chemical carcinogenesis, the expression of cyclin D1 and cyclin E was analyzed by RT-PCR and immunohistochemical studies in N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. Cyclin D1 mRNA levels were increased 2.8-fold in 25 week (P < 0.05) and 6.8-fold in 45 week (P < 0.01) papillomas induced by NMBA, when compared with normal rat esophageal epithelium. Cyclin E mRNA levels were increased 6.2-fold in 25 week (P < 0.01) and 6.9-fold in 45 week (P < 0.01) papillomas. Immunohistochemical staining revealed exclusive nuclear staining of both cyclin D1 and cyclin E. Furthermore, there was a sequential increase in cyclin D1- and cyclin E-positive cells from normal epithelium, to preneoplastic lesions, to papillomas. These findings suggest that overexpression of cyclin D1 and cyclin E occur relatively early in rat esophageal tumorigenesis and participate in tumor progression in this model.