By analysis of pleural effusions from 200 patients, 25 cases of amylase-rich effusions were identified, for an overall incidence of 13 percent. Four of the 25 patients (16 percent) had evidence of pancreatitis. These patients had higher mean ratios of pleural fluid to serum amylase levels (18 +/- 6.3 [SEM] vs 4.8 +/- 1.3) compared to patients with nonpancreatic diseases (p = 0.003); all four exhibited a predominant pancreatic isoenzyme profile. Of the 21 patients with nonpancreatic amylase-rich effusions, lung cancer was the most commonly associated condition (8 patients). In 14 of the 21 patients in whom an isoenzyme profile was obtained, salivary-type amylase was predominant. Amylase-rich pleural effusions occur frequently, and pleural fluid isoamylase determination is specific for pancreatitis-associated effusions. The finding of a pleural effusion rich in salivary isoamylase should prompt an evaluation for carcinoma (particularly of lung primary), but may also be seen in other pleural inflammatory conditions.