In order to discriminate between malignant and benign effusions, the values of tissue polypeptide specific antigen,carcinoembryonic antigen and squamous cell carcinoma associated antigen were measured in the pleural fluid of 30 patients with neoplasm, 10 with tuberculous pleurisy, 10 with transudates due to congestive heart failure or cirrhosis, 29 with parapneumonic effusions and 23 with benign diseases other than tuberculosis and pneumonia. Carcinoembryonic antigen and tissue poly-peptide specific antigen levels in effusions due to neoplasms were significantly higher than those in effusions due to other diseases. The areas under Receiver Operating Characteristic curves for carcinoembryonic antigen and tissue polypeptide specific antigen determinations were 0.69 and 0.67, respectively. No significant differences were found in the pleural fluid squamous cell carcinoma associated antigen levels between neoplasms and other diseases. The ability of tissue polypeptide specific antigen and carcinoembryonic antigen to discriminate between benign and malignant effusions may be considered comparable. Although both carcinoembryonic antigen and tissue polypeptide specific antigen showed a low accuracy (the number of undiagnosed pleural effusions is considerably high), both tissue polypeptide specific antigen and carcinoembryonic antigen determinations may contribute to a correct diagnostic classification. Moreover, the combination of these markers provides a specificity of 97.2%. However, the low number of positivities obtained for tissue polypeptide specific antigen and carcinoembryonic antigen together (13 cases in our series) reveals the need for further investigations.