This study was performed to investigate the phospholipase A2 (PLA2) serum activity in patients with chronic pancreatic disease. PLA2, elastase-1, total, and pancreatic isoamylase were evaluated in 40 control subjects, 28 patients with pancreatic cancer, 51 with chronic pancreatitis, and 36 with extrapancreatic diseases, mainly of gastrointestinal origin. Elastase-1, PLA2, and pancreatic isoamylase were increased in 56%, 25%, and 15% of patients with pancreatic cancer, and in 40%, 31%, and 41% of subjects with chronic pancreatitis. All four enzymes gave pathological values in a number of patients with extrapancreatic diseases. We conclude that the diagnostic efficacy of phospholipase A2 in chronic pancreatic disease is similar to that of other well known pancreatic enzymes, with an unsatisfactory sensitivity and specificity.