Plasma neurotensin concentrations are markedly elevated in patients with severe exocrine pancreatic insufficiency. We therefore investigated whether the exocrine pancreatic function could influence postprandial neurotensin plasma concentrations. Subsequently, we tested the hypothesis that this peptide hormone is involved in regulation of pancreatic secretion. When pancreatic juice is diverted from modified Herrera fistulas in dogs, a simultaneous application of physiological amounts of lipase reduces the elevated plasma neurotensin concentrations. On the other hand, immunoneutralisation of the circulating neurotensin inhibits pancreatic secretion. This suggests a physiological role of neurotensin in the regulation of the exocrine pancreas via an entero-pancreatic axis.