This prospective study evaluated the radiographic, endoscopic, histologic, and clinical characteristics of nodular duodenitis found in 17 of 50 (34%) patients with end-stage renal disease. By comparison, nodular duodenitis was noted in only 23 of 557 (4%) consecutive endoscopies in a general medical population. Endoscopic nodular duodenitis consisted of two or more nodules, 2.5-7.0 mm in diameter, with apical erythema, with or without tip erosions. Eight patients had nodules in the bulb only, eight had diffuse duodenal nodules, and a single patient had nodules only in the second portion of the duodenum. Singlecontrast barium x-rays were sensitive in detecting the nodules only when they were 5 mm or greater in diameter. Some degree of inflammatory infiltrate was found in 14 of 17 (82%) of the patients with nodular duodenitis; 10 of 17 had a moderate to severe histologic grade compared to 3 of 18 (P=0.015) patients with a normal endoscopic appearance to the duodenum. Several patients with endoscopic nodular duodenitis, in whom biopsies were taken both of the nodule and surrounding mucosa, were found to have a focal histologic lesion which consisted of villous blunting and thickening due to fibrosis and a chronic inflammatory infiltrate or lymphoid aggregate in the stroma. A higher incidence of peptic ulcers occurred in the nodular duodenitis group (3 of 17) compared to the remainder of the group (0 of 33) during a mean follow-up of 38 months (P=0.03). Resolution of the nodules occurred in six patients following successful renal transplant (four patients) and following vagotomy and pyloroplasty (two patients). These findings would suggest that nodular duodenitis, in patients with end-stage renal disease, represents a subset of duodenitis with a characteristic radiographic, endoscopic, and histologic appearance. © 1983 Plenum Publishing Corporation.