The aim of this study was to evaluate the frequency of a thickened subepithelial collagen band in the colon, its relationship to diarrhea, and the clinical relevance of its detection. During a 3.5 year period (May 1985-January 1989), a total of 3,323 biopsy specimens were obtained during 6,254 colonoscopies. A subepithelial collagen thickening greater than 10 microns was found in 40 patients (1.5 percent of the patients). Further assessment of these 40 patients showed that this histological lesion was characterized by a frequent association with chronic diarrhea (in 36 patients, i.e. 90 percent) whatever the cause, with diseases such as diabetes mellitus (8 cases) or inflammatory arthropathies (6 cases) and with a microscopic colitis in all cases. Course of collagen thickening was variable and independent of clinical course. Diarrhea was a constant finding when the collagen thickening was greater than 15 microns and frequently improved (12 patients/14) during treatment with Collagenan. This study suggests that a subepithelial thickened collagen band is an uncommon change in the colon and is frequently associated with chronic diarrhea. The significance of this morphological change is unknown, and its contribution to the pathogenesis of the diarrhea remains questionable.