Retinoids are vitamin A analogs that regulate growth and differentiation of squamous epithelial cells in vitro and in vivo. We examined the effects of retinoic acid (RA) and N-(4-hydroxy-phenyl) retinamide (HPR) on the growth properties of esophageal squamous carcinoma cell lines, and found that both RA and HPR induce morphological changes and inhibit growth. Immunofluorescence studies suggest alterations in keratins as a result of treatment with RA or HPR. In order to determine underlying molecular mechanisms, we found that RA or HPR did not induce arrest of cells in the G1 phase nor did treated cells undergo apoptosis. However, RA and HPR treatment did result in the downregulation of epidermal growth factor receptor (EGFR) which is known to bind key proproliferative ligands, such as epidermal growth factor and transforming growth factor alpha.