A regional heterogeneity of the responsiveness to neurohumoral agents has been demonstrated in proximal and distal colon. The aim of this study was to compare the motor responsiveness of circular and longitudinal muscles from ascending and sigmoid colon to carbachol and neurotensin. Ascending colon circular muscle was more sensitive to carbachol than sigmoid colon circular muscle (P < 0.05). Moreover, the potency for the carbachol-stimulated contraction was greater in ascending colon circular than longitudinal muscle (P < 0.05). The potency for carbachol and neurotensin stimulations was similar in longitudinal and circular muscles of both sections, respectively. However, the ascending colon circular muscle had a greater potency to neurotensin than longitudinal muscle (P < 0.03). Longitudinal muscle was more sensitive to the effects of neurotensin in sigmoid than ascending colon (P < 0.01). On a molar basis, neurotensin was approximately fivefold more potent than carbachol in producing similar contractions. These data suggest that these agents stimulate human colon smooth muscle according to region and type of muscle layer.