 Total proctocolectomy and ileal pouch-anal anastomosis is the surgical treatment of choice for patients with medically refractory ulcerative colitis, ulcerative colitis with dysplasia or cancer, and patients with familial adenomatous polyposis. Pouchitis, an inflammatory process of the ileal pouch, is the most common long-term complication. Increased stool frequency, abdominal pain, and pelvic discomfort are suggestive of pouchitis, approximately 40 of patients with these symptoms have no or minimal inflammation of the pouch or rectal cuff on endoscopy and histopathology. These patients have a condition resembling irritable bowel syndrome IBS, which we termed the irritable pouch syndrome IPS. The RATIONALE and FEASIBILITY for the proposed study are: 1 IPS occurs in a substantial number of patients with IPAA, significantly affecting the quality of life. However, IPS is rare in the general population, and is considered an orphan disease. Studies such as those we propose can only be conducted in centers with a large number of patients with IPAA. The Cleveland Clinic has maintained the worlds largest ileal pouch registry, with a total of more the 2,500 patients; 2 a series of investigations on the diagnosis and treatment of patients with inflammatory or functional diseases of IPS, notably the initial study of IPS, have been conducted by our team; 3 In contrast to IBS, the pathophysiology and treatment of IPS have not been studied. Our HYPOTHESES are that 1 similar to IBS, visceral hypersensitivity may play a role in the pathogenesis of IPS, and 2 amitriptyline, a safe and effective agent for patients with IBS, will be more effective than placebo in alleviating symptoms and improving quality of life in patients with IPS. The AIMS of the study are to 1 investigate visceral hypersensitivity using barostat examination of the pouch; 2 conduct a randomized, placebo-controlled clinical trial evaluating the use of amitriptyline in IPS. 