Two hypotheses have been proposed to explain the pathogenesis and cause of the increased subepithelial collagen deposition that occurs in patients with collagenous colitis, a rare disease of unknown cause. One hypothesis considers an inflammatory origin, and the other, a local abnormality of collagen synthesis. An analysis of clinical, endoscopic, and histologic findings from one of our patients and from previously published cases suggests that collagenous colitis is a form of inflammatory bowel disease characterized by localization of the initial injury to the superficial subepithelial zone and with subsequent fibrosis in that area. The data show a spectrum of clinical and histologic changes that represent different stages in the evolution of the inflammatory process.