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The changes of plasma pancreatic polypeptide (PP) and the relationship between PP response and exocrine pancreatic function in chronic pancreatitis are reported. In 260 healthy control subjects, plasma PP levels increased gradually with aging. Basal levels of PP in 30 patients with chronic pancreatitis were significantly lowered in comparison with age matched control subjects (control 95.0 +/- 10.3 pg/ml, chronic non-calcifying pancreatitis 45.0 +/- 7.3 pg/ml, chronic calcifying pancreatitis 40.4 +/- 6.0 pg/ml). Plasma PP response by insulin induced hypoglycemia, test meal ingestion, and pancreozymin-secretion represented a significant decrease in patients with chronic pancreatitis. Additionally, maximum PP response, especially in pancreozymin-secretin injection, had a good correlation with exocrine pancreatic function. These results suggest that the determination of plasma PP response is useful for the diagnosis of chronic pancreatitis.