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Causes of chronic watery diarrhea are multiple. There is not definite scientific evidence about which are the recommended explorations to be performed in the diagnostic workup of patients with functional diarrhea. The aim was to assess prospectively the presence of gluten-sensitive enteropathy, bile acid malabsorption, and sugar malabsorption in consecutive patients with chronic watery diarrhea of obscure origin fulfilling Rome II criteria of functional disease.A total of 62 patients with chronic watery diarrhea, defined as more than 3 loose or liquid bowel movements a day for at least 4 wk and a stool weight >200 g/day were included. The following tests were performed: (a) HLA-DQ2/DQ8 genotyping, and if positive, endoscopic biopsies from distal duodenum were obtained, and intestinal damage assessed; (b) SeHCAT (Se-homotaurocholate) abdominal retention test; (c) small bowel follow-through; and (d) hydrogen breath test (lactose, fructose + sorbitol). Gluten- or sugar-free diet, or cholestyramine was administered according to results. Functional disease was diagnosed if all tests performed were normal or if either there was no response to specific therapy or diarrhea relapsed during a 12-month follow-up.Bile acid malabsorption was considered to be the cause of diarrhea in 28 (45.2%) patients, sugar malabsorption in 10 (16.1%), gluten-sensitive enteropathy in 10 (16.1%), and both bile acid and sugar malabsorption in 2 patients. Twelve (19.4%) patients remained without a specific diagnosis and were considered as functional bowel disease. Diarrhea stopped in the 50 patients after specific treatment, decreasing the daily stool number from 5.4 ± 0.3 to 1.5 ± 0.1 (P < 0.0005), without relapse after the 12-months follow-up.The diagnosis of functional disease in patients with chronic watery diarrhea should be performed with caution since in most cases there is an organic cause that justifies diarrhea.