Formalin-fixed paraffin-embedded material of 158 diffuse malignant pleural mesotheliomas (DMPMs) was used in order to determine the differential diagnostic value of immunocytochemical probes against 9 different antigens. While vimentin expression was found in only 50% of cases, regardless of their histological subtype all tumours were found to be cytokeratin-positive when an antibody with broad-spectrum cytokeratin reactivity was used. Conversely, none of the cases was immunostained by antisera against carcinoembryonic antigen (CEA), Leu-M1 antigen, chromogranin A, S-100 protein, lysozyme and a T-cell associated antigen. The density of inflammatory cell infiltrates reactive with antisera agains the three latter antigens was not associated with the clinical behaviour of the neoplasms examined. Eight DMPM cases showed immunoreactivity with HEA-antibodies against Egp 34, an antigen previously supposed only to be expressed by carcinomas. On the basis of these findings, the consistent cytokeratin reactivity, also of the sarcomatous type of DMPM, may help to exclude metastatic involvement of the pleura by a mesenchymal neoplasm of other origin. CEA and Leu-M1 staining of a given pleural tumour, on the other hand, is indicative of a carcinoma secondarily afflicting the pleura, thus making the diagnosis of primary DMPM unlikely.