Objective: The present study aimed to examine the mesothelial cell properties in different types of benign and malignant pleural effusions by measuring pleural CA-125 levels. Design: In this retrospective study, pleural fluid was collected from 326 patients and pleural CA-125 levels were measured by radioimmunoassay. Patients were classified into five groups according to the etiology of pleural effusions: I, tuberculosis; II, malignant; III, pyogenic; IV, congestive heart failure; V, hepatic hydrothorax. Results: CA-125 levels were significantly higher in the malignant group than in all benign groups. There was no difference in pleural CA-125 levels between transudate and exudate benign etiologies. Although pleural CA-125 levels were significantly higher in malignant than benign effusions, about one-third of malignant pleural effusions had levels ＜600 U/mL. Among malignancies, there were no significant differences in pleural CA-125 levels between histologic types. Conclusion: CA-125 levels in benign pleural effusions may not be influenced by pleural inflammation, or hydrostatic or oncotic pressure changes. Pleural CA-125 levels are not influenced by the histological tumor type in malignant pleural effusions, suggesting that mesothelial cell properties are not altered by these factors in the pleural space.