We reviewed 327 patients with pleural effusion who had been examined at our department for identification of its cause during the 14 years between 1974 and 1987, and studied the percentages of definitive diagnosis by examining the pleural fluids of patients with malignant tumor and tuberculosis. We also measured the levels of carcinoembryonic antigen (CEA) and adenosine deaminase (ADA) in the pleural fluids of these patients and evaluated their diagnostic usefulness. We further carried out a detailed clinical study of the factors affecting the CEA and ADA activities in the pleural fluids, which are considered to be particularly important in differential diagnosis of patients with pleural effusion. Of 327 patients with pleural effusion, malignancy-related pleurisy was observed in 166 patients (50.8%), and tuberculous pleurisy in 85 (26.0%). The rate of definitive diagnosis based on the examination of the pleural effusion in these patients indicated that 20-30% of them pose difficulty in clinical diagnosis. CEA was positive in 64.7% of patients with malignancy-related pleurisy, and ADA was positive in 97.7% of those with tuberculous pleurisy. These suggested their usefulness as supportive diagnostic methods of those diseases. In addition, CEA was elevated in patients with complications such as empyema, suggesting an effect of non-specific cross-reacting antigen (NCA). ADA showed high values in patients with conditions related to cell-mediated immunological responses as well as empyema and hemolysis. It suggested the release of ADA from blood cells due to hemolysis. These factors must be carefully evaluated in the interpretation of the CEA and ADA activities in pleural effusion.