The pancreatic response to physiological concentrations of secretin obtained after minute boluses of exogenous secretin was studied in 16 normal volunteers. Output of bicarbonate into the duodenum was measured by duodenal aspiration in 5 subjects and by endoscopic cannulation of the pancreatic duct in 11 subjects. Pure natural porcine secretin was injected intravenously in doses of 125, 250, and 500 fmol x kg-1 body weight (0.0013, 0.0027, and 0.0054 clinical units x kg-1). All three doses of secretin increased plasma secretin concentration, duodenal bicarbonate concentration, and duodenal bicarbonate output significantly. The bicarbonate output measured by the two techniques did not differ significantly. The increments in median plasma secretin concentration were 1.6, 3.0, and 6.4 pmol x 1(-1) after secretin, 125, 250 and 500 fmol x kg-1, and the corresponding 15-min bicarbonate output 283, 442, and 1435 micromol, respectively. The concentrations of secretin in plasma found after these doses of secretin are of the same order of magnitude as the secretin concentrations found during physiological conditions in man. It is concluded that the physiological concentrations or secretin influence pancreatic bicarbonate secretion.