There is an increasing body of evidence suggesting regional heterogeneity in human colonic function. Using circular and longitudinal muscle strips from proximal and distal human colon, the present study sought to determine whether such regional differences were apparent in smooth muscle responsiveness to neurohumoral agents. Both proximal and distal muscle gave quantitatively similar responses to acetylcholine, as they did for noradrenaline. However, the circular muscle of the distal colon was more sensitive to vasoactive intestinal peptide than was the circular muscle of the proximal colon. Longitudinal muscle from both regions was comparatively insensitive to VIP.