Because the role of tachykinin receptors in colonic peristalsis remains incompletely understood, we studied the effect of tachykinin receptor antagonists on mouse colonic peristaltic activity. Peristaltic activity was assessed by quantifying the amplitude and interval of distension-induced pressure waves in proximal and distal colon segments of mice using a modified Trendelenburg set-up. We studied the effect of the NK₁, NK₂ and NK₃ tachykinin receptor antagonists RP67580 (2 mM), nepadutant (1 mM) and SR142801 (0.3 mM) respectively. Gradual distension of proximal and distal colon segments induced repetitive rhythmic pressure waves which were blocked by tetrodotoxin (1 mM) and virtually abolished by hexamethonium (0.1 mM) demonstrating their neuronal origin. The NK₁ receptor blocker RP67580 significantly reduced the amplitude of the pressure waves in segments of proximal (5.90.7 to 1.80.8 cmH₂O, n=7) and distal (4.80.6 to 1.50.7 cmH₂O, n=6) colon. RP67580 significantly reduced the interval in the proximal (667 to 876 s, n=5) but not in the distal colon. The NK₂ receptor blocker nepadutant significantly reduced the amplitude (5.20.5 to 3.30.7 cmH₂O, n=7) and the interval (527 to 396 s, n=7) in the proximal colon without affecting peristaltic parameters in the distal colon. Blockade of NK₃ receptors by SR142801 did not affect the amplitude or interval of peristaltic waves in the proximal and distal colon. Combined blockade of NK₁, NK₂ plus NK₃ receptors significantly reduced the amplitude in the proximal colon (6.50.9 to 1.60.8 cmH₂O, n=6) and prolonged the interval (635 to 10622 s, n=6). Our study shows that mouse colonic peristaltic activity has a strong tachykininergic component that is mediated mainly by NK₁ receptors and to a lesser extent by NK₂ receptors. We could not demonstrate a role for NK₃ receptors.