In a prospective clinical trial, 85 patients with acute pancreatitis, including 50 with acute interstitial-edematous pancreatitis and 35 with necrotizing pancreatitis, were recruited. Serum pancreatic immunoreactive phospholipase A2 (IR-PLA2), serum phospholipase A catalytic activity (CA-PLA), and serum phospholipase A2 catalytic activity (CA-PLA2) were determined daily between day 1 and day 10 after the onset of the disease. The serum course of IR-PLA2 values for patients with acute interstitial-edematous pancreatitis was comparable to that for patients with necrotizing pancreatitis. In contrast, the determination of CA-PLA and of CA-PLA2 specific activity in the serum revealed a high differentiation between patients with interstitial edematous and those with necrotizing pancreatitis. The overall accuracy for differentiating patients with necrotizing pancreatitis from those with the interstitial-edematous type was 79% for CA-PLA and 77% for CA-PLA2 (cut-off level: CA-PLA, 15 U/L, day 1-5; CA-PLA2, 3.5 U/L, day 1-5). Patients with pancreatitis-associated pulmonary complications showed significantly higher CA-PLA and CA-PLA2 values in the serum. This study demonstrates the role of serum catalytic phospholipase A2 in human acute pancreatitis where the development of pancreatic necrosis and pulmonary failure is concerned.