The nature of epithelial cell cytokeratins from epidermal basal cell carcinomas (BCC) (8 cases) and squamous cell carcinomas (SCC) (5 cases) was investigated by biochemical and immunological analysis. Cytokeratin proteins were extracted with high salt buffer and triton X 100 and were comparatively analyzed by SDS (sodium dodecyl sulphate) polyacrylamide gel electrophoresis. Both types of tumor showed either an absence or a very low amount (5% of the total protein) of the major protein band (MW 67000) present in normal human epidermis. This correlated well with results of immunolabelling showing that 67000 keratin antisera, only reacted with some dyskeratotic cells in sections of these tumors. Gel electrophoresis showed in BCC and SCC, three distinct groups of predominant polypeptide bands of apparent relative MW: (1) 60-62000 (2) 54-56000 and (3) 49000, representing respectively about 43.0%, 31.0% and 20.4% of the total proteins. Antibodies raised in animals against polypeptide bands C1 (MW 62000), C2 (MW 56000) and C3 (MW 49000) from SCC, strongly labelled (indirect immunofluorescence) all malignant cells present in the 2 kinds of tumors. These antisera showed a preferential reaction with the basal epithelial cells, in sections of human and animal epidermis and mucosa thus, suggesting numerous common antigenic determinants between epithelial cells from diverse origins. On the other hand, strong differences between mucosal and epidermal upper layers were noted with C1, C2, C3 and 67000 antisera. These results are further evidence for the existence of different pathways of keratinization in epidermis and mucosa.