Differentiation of diffuse malignant mesothelioma (DMM) from pleural carcinomatous metastases, e.g., of lung cancer (LC) may be difficult both for the clinician and the pathologist [1, 2] because of the limited diagnostic accuracy of radiologic criteria and conventional light microscopy including histochemistry [3,4]. Immunohistochemical detection of carcinoembryonic antigen (CEA) in tumor biopsy material has been shown to be a valuable diagnostic adjunct, as DMMs, unlike LCs and other carcinomas, express this antigen only rarely (9-11%) [5]. In some cases, however, the only method of obtaining suitable biopsy material is by open thoracotomy [2, 6]. Moreover, immunohistochemical examinations are expensive and not generally readily available. We therefore decided to find out what conclusions may be drawn from the much simpler determination of CEA levels in serum and in pleural effusion fluid (EF).We measured CEA in serum and EF using our own, and five commercially available radioimmunoassays or enzyme immunoassays (Abbott, Behringwerke, CIS, Roche, Pharmacia) with a serum level of 3 mg/L as the upper limit of reference values. In an initial partly retrospective study (learning phase), we examined patients with histologically proven DMM (n = 94) or LC (n = 79). Using ROC analysis, cutoff levels (serum CEA: 5.2 rag/L, EF CEA: 4.5 mg/L) were set so as to produce the most statistically significant differentiation (x2-test) between DMM and LC ( Table 1). The discrimination values specified and published [7] after the learning phase were then evaluated in a strictly prospective fashion in two additional sets of patients. From 1991 to 1992, we determined serum and EF CEA levels in 146 patients participating in the multicentric German DMM study, in all of whom the diagnosis of DMM had been reviewed by a panel of experienced pathologists. For comparison, we analyzed 124 patients who had presented with pleural effusions of unknown aetiology and had subsequently been shown to be suffering from metastatic carcinoma. There was a statistically significant difference between the DMM and the metastatic carcinoma group in terms of the frequency of elevated CEA levels (x2-test, p < 0.01) ( Table I). These results show that simple determination of CEA provides information that is useful for distinguishing between DMM