The investigation concerned the effects of neurotensin on mechanical activity of isolated rat proximal colon. An isometric-isovolumic preparation was used. Colonic segments showed spontaneous contractile activity, consisting of regular changes in both endoluminal and isometric tension. Neurotensin (1 pM to 0.1 microM) induced a concentration-dependent tonic contraction of both circular and longitudinal muscle accompanied by high frequency oscillatory activity. Desensitization of the neurotensin receptors antagonized the contractile activity of neurotensin. The excitatory effects of neurotensin were partially blocked to the same degree by tetrodotoxin and atropine, indicating that a component of the neurotensin-mediated contraction involves the release of endogenous acetylcholine. The tetrodotoxin-resistant component of the neurotensin-induced effect seems to be due to a direct action on the smooth muscle cells.