Serum immunoreactive trypsin (IRT) response to secretin injection was studied in 13 patients with chronic pancreatitis with different degrees of exocrine dysfunction and in 10 control subjects. The maximal increase of serum IRT from basal values and the integrated trypsin output (ITO) after secretin administration were significantly correlated with the output of chymotrypsin into the duodenum during caerulein-secretin infusion (p < 0.01), but not with the output of lipase nor of bicarbonate. Serum IRT response to secretin stimulation was greater in 4 of the 5 patients with chronic pancreatitis with mild to moderate exocrine dysfunction than in the control group, suggesting an increased regurgitation of IRT into the blood stream by the pancreas, probably due to some degree of obstruction to pancreatic secretory flow in absence of severe acinar cell damage. Conversely, the response of serum IRT after secretin administration in 7 of the 8 patients with severe exocrine pancreatic deficiency was lower than in control subjects, probably because of the advanced distruction of the acinar pancreatic tissue. The response of serum IRT to secretin stimulation seems to vary following pancreatic function impairment and might reflect the degree of pancreatic exocrine dysfunction in chronic pancreatitis.