Hyaluronic acid (HA) was determined with a radiometric assay in the serum and pleural fluid of 85 patients with pleural effusions, including 15 with malignant mesothelioma, 32 with other cancer, 31 with nonmalignant inflammatory diseases, and seven with congestive heart failure. With a cutoff level at 100 mg/L, the pleural fluid concentration of HA was raised in 73 percent of patients (11 of 15) with malignant mesothelioma and in 23 percent with nonmalignant inflammatory diseases, but in none with other cancer and in none with congestive heart failure. The median concentration of pleural fluid HA was significantly higher in patients with mesothelioma than in those with other cancer (p less than 0.005). Determination of carcinoembryonic antigen (CEA) in pleural fluid further helped to differentiate between mesothelioma and other types of cancer; concentrations of CEA above 10 micrograms/L were found in four of 15 (27 percent) patients with mesothelioma, but in 38 percent of the patients with other cancer. We concluded that in the differential diagnosis of pleural effusions associated with malignant tumors a high concentration of HA in pleural fluid combined with a low concentration of CEA suggests malignant mesothelioma as opposed to other types of cancer.