The distribution of keratin proteins and carcinoembryonic antigen (CEA) in 20 diffuse pleural malignant mesotheliomas and 20 adenocarcinomas of the lung was determined with the use of an indirect immunoperoxidase method. Keratin proteins were identified in all of the mesotheliomas, with strong staining observed in 17 of the cases. Tumor cells of various histologic types (tubular, papillary, solid, and spindle) revealed staining for keratin proteins. A variety of staining patterns were observed, but the homogeneous pattern predominated, in either a diffuse (16 cases) or focal form (4 cases). CEA was usually absent (11 cases), but weak or equivocal staining was also observed (8 cases), and 1 case uniquely exhibited moderate staining for CEA. In contrast, adenocarcinomas of the lung usually stained weakly or negatively (18 cases) for keratin proteins and exhibited a predominantly peripheral staining pattern. All cases, however, stained strongly or moderately for CEA. The profile of strong keratin staining and weak or absent CEA staining appears characteristic of mesotheliomas and may be diagnostically useful in defining the epithelial element of these neoplasms and in distinguishing them from adenocarcinomas.