A clinical and biochemical analysis of 27 attacks of acute pancreatitis was made throughout the course of the disease. In severe attacks alpha 2-macroglobulin (alpha 2-M) decreased during the first days, reaching values in blood below 40% of the normal value. In addition, this remaining alpha 2-M had a decreased trypsin-binding capacity, indicating circulating alpha 2-M protease complexes. The inter-alpha-trypsin inhibitor concentration was also decreased, whereas alpha 1-proteinase inhibitor, antichymotrypsin, and pancreatic secretory trypsin inhibitor increased. All changes were most pronounced in the peritoneal fluid and were also closely correlated to the severity of the disease, assessed by both Ranson's and McMahon's classification systems. All patients with clinical complications had profound biochemical changes. In accordance with earlier findings, activation of both the complement and kinin systems seems possible in both blood and peritoneal fluid at the low alpha 2-M concentrations found in severe attacks.