Neurotensin (1-100 nM) produced an inhibitory effect and an excitatory effect on the peristaltic activity elicited by intraluminal distension using the Trendelenburg method or the intraluminal perfusion method in isolated segments of guinea-pig small intestine. The relative contribution of these effects to the overall effect varied from one region to another of the small intestine. In the Trendelenburg preparation, the excitatory effect was found to be accompanied by a decrease in the threshold intraluminal pressure required to trigger a peristaltic reflex. A substantial difference between the jejunum and the ileum was noted in that neurotensin-induced stimulation of peristaltic activity was observed in a smaller number of the segments in the jejunum than in the ileum. A nonpeptide neurotensin receptor antagonist, SR 48692, 2-[(1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl) pyrazol-3-yl)carbonylamino]tricyclo(3.3.1.1.(3.7))decan++ +-2-carboxylic acid (90 nM), abolished both the inhibitory and excitatory effects. Apamin (10 nM) abolished the inhibitory effect. From these results, neurotensin appears to exert both excitatory and inhibitory actions, via its receptors sensitive to SR 48692, on peristaltic activity in guinea-pig small intestine. The excitatory action varies with an increasing gradient toward the terminal end of the small intestine, and the inhibitory action involves apamin-sensitive mechanism.