Cytokeratin expression in rat lung tumors was studied using polypeptide-specific monoclonal antibodies (MAbs) to human cytokeratins 4, 5, 7, 8, 10, 13, 14, 18 and 19. Experiments were performed on tumor fragments derived from 5 experimental rat squamous-cell lung tumors and one adenocarcinoma, as well as on cell lines obtained from the same tumors. The aims of this study were to investigate the differentiation profile of the rat tumor tissue and established tumor cell lines based on light and electron microscopical features and on cytokeratin phenotype, to characterize the tumor type and degree of differentiation of the lung tumors maintained during passaging in experimental animals, and to compare the cytokeratin expression pattern in transplanted tumors with that of the cultures derived from these tumors. Our results indicate that, in general, the antibodies used cross-react with rat cytokeratins and that these MAbs can be used to phenotype rat lung carcinomas. Both the tumor fragments and the cultured cells revealed a similar pattern of cytokeratin expression. In addition, the degree of differentiation was maintained upon prolonged culturing in vitro. MAbs to cytokeratin sub-types can therefore be used to distinguish the main sub-types of rat lung tumors and can give an indication about the degree of differentiation.