This project proposed to morphologically define the mechanism of action of vitamin A and its derivatives (retinoids) in altering epidermal differentiation in normal skin, and in benign and malignant lesions of skin. Topical all-trans retinoic acid, but not systemic 13-cis-retinoic acid, increased gap junction density and decreased desmosome density in treated basal cell carcinomas. This indicates that topical and systemic retinoids may exert their antineoplastic activity by different cellular mechanisms.