Epidermal differentiation is a genetically programmed sequence of morphological and functional events in which there is a rapid turnover of distinct cell populations. In other tissues, alterations in the cell membranes have been found to be associated with stages of differentiation and with neoplasia; it has been further postulated that cell membranes may play a key role in the regulation of differentiation. Populations of epidermal cells have been separated on gradients of Percoll. The cell surfaces of undifferentiated and differentiating normal epidermal cells, of basal cell carcinoma, and of a carcinogen-transformed epidermal cell line have been studied by lactoperoxidase-catalyzed iodination followed by SDS gel electrophoresis. Similar studies will be carried with other cell suface markers, including lectins. Isolation of membranes of various cell types is in progress, to be followed by lectin-affinity chromatography to isolate differentiation and transformation markers. Purified glycoproteins will be injected into rabbits to produce antibodies. Radioimmunoassays will also be used to measure the cross-reactivity of antibodies and antigens drawn from different cell populations, normal and neoplastic. The overall aim is to characterize surface glycoproteins, and to explore distinctions among glycoproteins, from normal cell populations at various stages of differentiation and from carcinomas, that might serve as markers of these populations.