A clinical syndrome of chronic colitis unique to the sigmoid colon harboring diverticular was recently reported; its histopathological appearance has not been fully elucidated. In this study, the authors analyzed the clinical and pathological features of 23 patients (age range, 38-87 years; median age, 72 years) with diverticular disease-associated chronic colitis. Nineteen presented with hematochezia; four had abdominal pain. Colonoscopic visualization of the mucosa showed patchy or confluent granularity and friability affecting the sigmoid colon encompassing diverticular ostia. Colonic mucosae proximal and distal to the sigmoid were endoscopically normal. Mucosal biopsy specimens showed features of idiopathic inflammatory bowel disease that included plasmacellular and eosinophilic expansion of the lamina propria (100%), neutrophilic cryptitis (100%) with crypt abscesses (61%), basal lymphoid aggregates (100%), distorted crypt architecture (87%), basal plasmacytosis (61%), surface epithelial sloughing (61%), focal Paneth cell metaplasia (48%), and granulomatous cryptitis (26%). Concomitant rectal biopsies obtained in five patients demonstrated histologically normal mucosa. Fourteen patients treated with high-fiber diet or antibiotics or both improved clinically, as did nine patients administered sulfasalazine or 5-aminosalicylic acid. Five patients underwent sigmoid colonic resection, three for stricture with obstruction and two for chronic blood loss anemia. Among a control population of 23 age- and gender-matched patients with diverticular disease without luminal surface mucosal abnormality, none required resection during the same follow-up period. By Fisher's exact test, a statistically significant difference in outcome for patients with and without colitis was detected (p = 0.049). In addition, three patients developed ulcerative proctosigmoiditis 6, 9, and 17 months after the onset of diverticular disease-associted colitis. The data indicate that diverticular disease-associated chronic sigmoid colitis expresses morphological features traditionally reserved for idiopathic inflammatory bowel disease. Its clinical and endoscopic profiles permit distinction from Crohn's disease and ulcerative colitis. Patients with chronic colitis in conjunction with diverticula are at increased risk for sigmoid colonic resection. Diverticular disease-associated chronic colitis may also precede the onset of conventional ulcerative proctosigmoiditis in some cases.