Recent evidence has been collected by several investigators defining a distinct population of dendritic cells (Langerhans cells) of mesenchymal origin residing in the epidermal surfaces of many mammalian species. These cells play a dominant role in the processing of antigens presented through cutaneous surfaces and carry a Class II histocompatability antigen felt to be of central importance in the afferent arm of allograft rejection. They also possess many of the characteristics of macrophages active in the efferent arm of immunologic responses. An equivalent subset of dendritic cells (Langerhans cells) in ocular surface epithelium of the human, mouse rat, and guinea pig has been identified by enzyme histochemistry, immunofluorescence, and electron microscopy. Ocular surface Langerhans cells proliferate in the setting of corneal inflammation (remote and recent) and are depleted by topical and systemic corticosteroids. Ocular surface Langerhans cells may play a central role in ocular contact hypersensitivity, corneal allograft rejection, and ocular surface immune surveillance.