Patients with ulcerative colitis have decreased postprandial colonic contractions. The purpose of this study was to determine whether the smooth muscle from patients with ulcerative colitis responds abnormally in vitro to different stimuli. Circular colonic smooth muscle strips from patients with ulcerative colitis, acute diverticular disease, or adenocarcinoma were stretched to the optimal length and stimulated with electrical field stimulation (EFS), bethanechol, or increased concentrations of extracellular K+. The EFS-stimulated on-contraction was similar in each group, but the off-contraction was decreased in patients with colitis compared with patients with cancer (P less than 0.02) or diverticular disease (P less than 0.01). Bethanechol stimulated a dose-dependent colonic contraction, which was less in the strips from patients with colitis compared with cancer (P less than 0.02) or diverticular disease (P less than 0.05). The response to increased extracellular K+ was less in muscle from patients with colitis (P less than 0.01) than in the other tissues. Muscle from diverticular disease developed greater stress to K+ stimulation than did muscle from cancer (P less than 0.05). These studies suggest that there is a decrease in the force of muscle contraction in colonic muscle obtained from patients with colitis compared with normal muscle resected from patients with cancer or with muscle associated with diverticular disease of the colon. The similar relatively low amplitude of the on-contraction in each group suggests the physiological release of an inhibitory neurotransmitter.