The effects of neurotensin were investigated in intestinal smooth muscle preparations. Neurotensin relaxed the rat ileum, and contracted the guinea-pig ileum and taenia. Neurotensin induced a biphasic response (relaxation followed by contraction) in the contracted guinea-pig ileum. In all systems, half-maximal effects were obtained with 4--5 nM neurotensin and maximal responses with 30--60 nM; tachyphylaxis occurred with higher concentrations. Tetrodotoxin did not affect the responses to neurotensin in the rat ileum and the guinea-pig taenia. Tetrodotoxin abolished the contraction or the contraction phase (but not the relaxation phase) of the biphasic response induced by neurotensin in the guinea-pig ileum. Atropine partially inhibited the Neurotensin-induced contraction in the guinea-pig ileum. These results suggest that neurotensin acts on intestinal smooth muscle both directly (relaxation of the rat and guinea-pig ileum, and contraction of the guinea-pig taenia) and through a nerve-mediated, partly cholinergic, process (contraction of the guinea-pig ileum).