Neurotensin stimulates amylase release from dispersed pancreatic acini at concentrations as low as 10(-15) M. The naturally occurring fragments of neurotensin (NT), NT 1-8 and NT 1-11, also stimulate amylase secretion at concentrations that occur in peripheral plasma (10(-11) M). The analogue D-Phe11 neurotensin was as potent as neurotensin itself with respect to stimulation of amylase secretion. Basal plasma neurotensin levels were approximately 10 pmol/L, a concentration that stimulates the exocrine pancreas in vitro. Increases in plasma neurotensin levels induced by infusion of neurotensin caused greater increases in secretion of pancreatic amylase than did similar changes of neurotensin concentration in vitro. These results suggest that in addition to its direct action, other factors are involved in modulation of the effects of neurotensin on pancreatic exocrine function in vivo.