The effect of neurotensin on human pancreatic secretion and its role in the control of pancreatic function are not well defined. In the present investigation I have studied the effect of low doses of neurotensin on pure pancreatic secretion in six subjects with external transduodenal drainage of the main pancreatic duct performed after biliary tract surgery. Intravenous infusion of neurotensin at doses of 0.5 and 2.5 pmol X kg-1 X min-1, administered during submaximal pancreatic stimulation with secretin and cerulein, caused a significant and dose-dependent stimulation of pancreatic secretion (volume, bicarbonate, and protein). The effect of neurotensin was rapid, persisted for the duration of neurotensin infusions, and ceased immediately when the administration of the peptide was discontinued. Compared with control values, the increase in bicarbonate output averaged 24.8% and 44.8% and the increase in protein output 29.2% and 54% for the two different doses of neurotensin used, respectively. The clear effectiveness of the small doses of neurotensin used in the present study strongly suggests that the stimulatory effect of the peptide on pancreatic secretion may be of physiologic significance.