The effects of neurotensin on mechanical activity of rat duodenum were investigated using an isometric-isovolumic preparation. Neurotensin (1 pM to 10 nM) induced a concentration-dependent, tetrodotoxin (TTX)-insensitive fall in both endoluminal pressure and isometric tension. At higher concentrations of neurotensin (1 nM to 1 microM) the relaxation was followed by a concentration-dependent TTX-insensitive contraction, detected only by an increase in endoluminal pressure. Different concentrations of neurotensin were required to desensitize the relaxant and the contractile actions of the neuropeptide. The relaxation was antagonized by apamin, while the contractile response was blocked by nifedipine. Neurotensin, when tested separately on longitudinal and circular muscular strips, caused relaxation of the longitudinal strips. Circular strips showed contractions in response to neurotensin, following an inhibitory phase, if the strips were spontaneously or pharmacologically activated. The results suggest the presence of two sets of neurotensin receptors with a differential localization between the two muscular layers in rat duodenum.