Collagenous ileitis (CI), characterized by subepithelial collagen deposition in the terminal ileum, is an uncommon condition. The few cases reported to date have been associated with collagenous colitis (CC) or lymphocytic colitis. Thirteen cases of CI retrieved over a 9-year period were retrospectively studied. There were 7 female and 6 male patients, with an age range of 39 to 72 years (mean, 64 y). Two groups were identified: (1) CI associated with collagenous or lymphocytic disease elsewhere in the gastrointestinal tract and (2) CI as an isolated process. Diarrhea was the presenting symptom in 11 cases. Most patients had no regular medication use. Subepithelial collagen thickness ranged from 15 to 100 μm (mean, 32 μm) and involved 5% to 80% of the subepithelial region of the submitted biopsies. Six cases had >25 intraepithelial lymphocytes (IELs)/100 epithelial cells, and villous blunting was observed in 11 cases. Chronic inflammation of the lamina propria was present in 9 cases, and focal neutrophil infiltration was identified in 3 cases. In biopsies taken from other sites, 7 of 13 colonic biopsies showed CC, 4 of 9 gastric biopsies showed collagenous gastritis, and 2 of 10 duodenal biopsies were abnormal with collagenous sprue (n=1) and partial villous atrophy and increased IELs (n=1) (both celiac disease related). Resolution of the subepithelial collagen deposition was found in the 1 case in which follow-up of terminal ileal biopsies were taken. There was partial or complete resolution of symptoms in 6 of 9 patients for whom follow-up information was available.