The involvement of the tachykinins in extrinsic nervous control of motility was studied in isolated, vascularly perfused, porcine ileal segments. Substance P and neurokinin A (10(-8) M) stimulated motility, and nonpeptide NK1 and NK2 receptor antagonists (10(-6) M) abolished this. Electrical stimulation of the mixed extrinsic nerves (8 Hz) had no effect alone or with atropine (10(-6) M) or phentolamine (10(-5) M), but increased motility during coinfusion of both blockers. This effect was abolished by hexamethonium (3 x 10(-5) M), and was reduced by over 80% by the NK1 receptor antagonist. As previously shown, substance P and neurokinin A were released during nerve stimulation, only during blockade of alpha-adrenergic and muscarinic receptors, and the release was abolished by hexamethonium. Capsaicin infusions (10(-5) M) increased substance P and neurokinin A release, and weakly stimulated small intestinal motility, but this was not inhibited by the tachykinin antagonists. Our results suggest that intrinsic tachykinin-producing neurons, controlled by extrinsic, nicotinic, excitatory neural pathways, and extrinsic adrenergic, inhibitory pathways, participate in the regulation of small intestinal motility.