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Postprandial symptoms in irritable bowel syndrome are common and relate to an exaggerated motor and sensory component of the gastrocolonic response. We investigated whether this response can be affected by hypnotherapy.We included 28 patients with irritable bowel syndrome refractory to other treatments. They were randomized to receive gut-directed hypnotherapy 1 hour per week for 12 weeks (N = 14) or were provided with supportive therapy (control group; N = 14). Before randomization and after 3 months, all patients underwent a colonic distension trial before and after a 1-hour duodenal lipid infusion. Colonic sensory thresholds and tonic and phasic motor activity were assessed.Before randomization, reduced thresholds after vs. before lipid infusion were seen in both groups for all studied sensations. At 3 months, the colonic sensitivity before duodenal lipids did not differ between groups. Controls reduced their thresholds after duodenal lipids for gas (22 ± 1.7 mm Hg vs. 16 ± 1.6 mm Hg, p < .01), discomfort (29 ± 2.9 mm Hg vs. 22 ± 2.6 mm Hg, p < .01), and pain (33 ± 2.7 mm Hg vs. 26 ± 3.3 mm Hg, p < .01), whereas the hypnotherapy group reduced their thresholds after lipids only for pain (35 ± 4.0 mm Hg vs. 29 ± 4.7 mm Hg, p < .01). The colonic balloon volumes and tone response at randomization were similar in both groups. At 3 months, baseline balloon volumes were lower in the hypnotherapy group than in controls (83 ± 14 ml vs. 141 ± 15 ml, p < .01). In the control group, reduced balloon volumes during lipid infusion were seen (141 ± 15 ml vs. 111 ± 19 ml, p < .05), but not after hypnotherapy (83 ± 14 ml vs. 80 ± 16 ml, p > .20).Hypnotherapy reduces the sensory and motor component of the gastrocolonic response in patients with irritable bowel syndrome. These effects may be involved in the clinical efficacy of hypnotherapy in IBS.