The present study has been designed to work out the factors regulating the fasting serum levels of trypsin-like immunoreactivity in chronic pancreatitis. One hundred patients with chronic pancreatitis have been included and studied during a painless phase of the disease. No relationships have been observed between serum trypsin-like immunoreactivity and the presence of pancreatic calcifications. Serum immunoreactive trypsin levels showed a gradual decline parallel to the progressive impairment of bicarbonate and enzyme (trypsin and chymotrypsin) outputs in duodenal aspirates during pancreatic secretory studies. Therefore, serum trypsin-like immunoreactivity levels are thought to reflect the functional capacity of the exocrine pancreas. Reduced levels of trypsin-like immunoreactivity were detected in almost all patients with diabetes and steatorrhea. However, the finding of low levels also in a minority of chronic pancreatitis patients with normal endoscopic retrograde cholangiopancreatography or pancreatic secretory tests points to other factors which, in addition to the atrophy of the pancreatic parenchyma, may influence the circulating levels of trypsin-like immunoreactivity in chronic pancreatitis.