In the gastrointestinal tract, tachykinin NK₁ receptors are widely distributed in a number of neuronal and non-neuronal cells involved in the control of gut motor activity. In particular, in the rabbit isolated distal colon, which is a suitable model system to investigate the contribution of tachykinins as non-cholinergic excitatory transmitters, the influence of NK₁ receptors in the regulation of peristalsis is not known. The selective NK₁ receptor antagonists SR140333 (0.3 and 1 nM) and MEN10930 (0.3-10 nM) significantly enhanced the velocity of rabbit colonic propulsion to submaximal stimulation. The prokinetic effect of SR140333 was prevented by L-NNA, a nitric oxide synthase inhibitor, indicating that NK₁ receptors located on nitrergic innervation exert a functional inhibitory restraint on the circular muscle and probably on descending excitatory and inhibitory pathways during propulsion. Conversely, the selective NK₁ receptor agonist, septide (3-10 nM), significantly inhibited colonic propulsion. In the presence of L-NNA, the inhibitory effect of septide was reverted into a prokinetic effect, which is probably mediated by the activation of postjunctional excitatory NK₁ receptors.