The clinical usefulness of serum pancreatic secretory trypsin inhibitor (PSTI) in pancreatic diseases was evaluated. The mean serum PSTI level of 41 healthy normal persons was 9.4 ng/ml (ranging from 5.2 to 16.7 ng/ml). Serum PSTI levels were abnormally raised in all patients with acute pancreatitis ranging from 35.0 to 4500 ng/ml, but were almost within normal range in patients with chronic pancreatitis, pancreatic cyst, acute abdominal emergencies such as perforated ulcer and intestinal obstruction, and macroamylasemia. There was no correlation between serum PSTI levels and total or pancreatic-type isoamylase activity. Patients with acute pancreatitis in whom the elevation of serum PSTI was transient and occurred after that of serum amylase activity had relatively mild symptoms and recovered along with normalization of serum PSTI levels. On the other hand, patients whose serum PSTI values became increased coincidentally with serum amylase activity and remained elevated, had severe clinical symptoms and unfavorable clinical outcome. Of 2 patients who underwent partial pancreatectomy, the serum PSTI level increased markedly in one who developed postoperative pancreatitis but not in the other without pancreatitis. In contrast to patients with acute pancreatitis, the serum response to the secretin stimulation in patients with chronic pancreatitis, was only small and transient, reaching the maximum at 10 min after administration of secretin. These results suggest that measurement of serum PSTI concentration may be useful in the diagnosis of acute pancreatitis and that the degree of rise and the duration of the elevated levels of serum PSTI are closely related to the severity of acute pancreatitis.