Introduction:Chronic diarrhea is a common problem. The causes of chronic diarrhea are numerous.The subsets of patients are those having chronic non bloody diarrhea with normal colonoscopy. These patients may be challenging for the physicians in respect to diagnosis. Many of these patients might be diagnosed mistakenly as having irritable bowel syndrome. The aim of this study is to determine the causes of chronic diarrhea in this subset of patients.Material and Methods:This descriptive study encompassed all patients with chronic non-bloody diarrhea that had referred to Shariati Hospital clinic during an 11 month period (Nov 2003- Oct 2004). Routine laboratory tests, thyroid function test, small bowel transit, HIV test, celiac serology, and colonoscopy with biopsy were performed. Upper endoscopy with biopsy of second portion of the duodenum was performed also.Results: Sixty-five patients (34 males, with an average age of 39.6±16 Ys) were included in the study. 43 (66.2%) patients had Rome II criteria for irritable bowel syndrome IBS. Of these 43 patients, 38 (88.4%) patients had IBS and 5 (11.6%) patients had organic diseases (including 3 (7%) patients with microscopic colitis (MC) and two (4.6%) patients with malabsorption syndrome). Thirteen (20%) patients had organic diseases including 4 (6.2%) patients with MC, 5 (7.7 %) patients with malabsorption syndrome, and one (3.1%) patient with crohn disease. Seventy five percent of patients with MC also had Rome II criteria for IBS. The causes of diarrhea were not clarified in 14 (21.5%) patients.Overall, the most common organic causes of chronic diarrhea were malabsorption and MC.Conclusion: Prior to the diagnosis of IBS, in patients with chronic non bloody diarrhea who have normal colonoscopy, a colonic biopsy should be performed to rule out MC, and if normal, small bowel diseases should be suspected.