Pulmonary surfactant protein A (SP-A) is known to be a major phospholipid-associated glycoprotein in pulmonary surfactant, which is specific to the lung. Immunohistochemically, expression of SP-A in tumor tissues is found in approximately 50% of patients with lung adenocarcinoma but not in the other histologic types of lung cancer of metastatic lung tumors. In this study, the SP-A content of pleural effusions was determined using an enzyme-linked immunosorbent assay. These results showed that approximately 40% of patients with lung adenocarcinomas (27 of 67) had high levels of SP-A (greater than 500 ng/ml) in their pleural effusions. By contrast, patients with other histologic types of lung cancers, adenocarcinomas of different primary sites, and tuberculosis had low levels of SP-A in their pleural effusions. The determination of SP-A in malignant effusions will contribute to distinguishing primary lung adenocarcinoma from adenocarcinomas of miscellaneous origin.