Summary lntegrin expression is normally confined to the basal layer of the epidermis, but when epidermal homeostasis is perturbed, the receptors are also expressed by suprabasal, differentiating keratinocytes. We have used the involucrin promoter to express functional human integrin subunits a2, a5, and f3, in the suprabasal epidermal layers of transgenic mice. In mice expressing cc5 or f3, alone or a& or a& heterodimers, there were hair and whisker abnormalities and a failure of eyelid fusion. In addition, mice expressing PI alone or in combination with a2 or a5 exhibited epidermal hyperproliferation, perturbed keratinocyte differentiation, and skin inflammation, all of which are features of a common human skin disease, psoriasis.