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Nine patients (seven females, two males) with chronic watery diarrhea and nonspecific colonic mucosal inflammation followed for 1-5 yr are presented. Eight were diagnosed as having collagenous colitis on the basis of marked thickening of the subepithelial collagen layer in at least one set of biopsies. The thickness of the collagen table varied with time in all eight cases. When thickening was minimal, morphological features were indistinguishable from microscopic colitis, signifying that, in most cases, collagenous colitis and microscopic colitis are part of the same spectrum of colonic mucosal response. One of the eight patients had documented collagenous colitis and gluten-associated enteropathy for 12 yr. The colitis and duodenal histology improved synchronously when a gluten-free diet and corticosteroids were administered. The ninth patient had microscopic colitis and enteropathy which did not respond to gluten withdrawal. This patient never exhibited thickening of subepithelial collagen in repeated biopsies over 5 yr, suggesting that an entity of microscopic colitis may exist independent of collagenous colitis. Duodenal mucosal biopsies showed normal histology in four other patients with collagenous colitis. The histological variability of collagenization and inflammation during the course of collagenous colitis and microscopic colitis and the clinical feature of watery diarrhea suggest that these two entities be grouped together as the watery diarrhea-colitis syndrome. [ABSTRACT FROM AUTHOR]