To assess the relation between circulating cathodic trypsinogen (CT) levels and exocrine pancreatic function, and to compare the radioimmunological with the enzymatic measurement of duodenal trypsin, we evaluated exocrine pancreatic function in 34 controls and in 32 patients with proven chronic pancreatitis (CP). There was no relation between CT and the volume rate of pancreatic secretion, nor did serum CT levels correlate with the concentration output of duodenal bicarbonate in controls. However, in CP patients, there was a low value of the correlation coefficient. A good relationship between serum CT levels and duodenal trypsin secretion was detected when the trypsin content was expressed as the mean value of both concentration and output. The enzymatic estimation of duodenal trypsin was related closely to its radioimmunological measurement, but there was better correlation of serum CT to duodenal immunoreactive than to enzymatic trypsin. In patients with CP, low levels were observed in 29% of cases with serum CT estimation, in 75% with duodenal bicarbonate, and in 63% and 79% with enzymatic and immunoreactive trypsin outputs, respectively. We conclude that serum CT levels may reflect the functioning mass of pancreatic acinar cells and that in assessing pancreatic secretory capacity, the immunoreactive measurement of trypsin excretion is more sensitive than the enzymatic measurement and as accurate as bicarbonate output.