Previous reports have suggested that endoscopic evaluation, with histological and microbiological examination of biopsied tissue, is required to diagnose gastrointestinal disease accurately in patients after allogeneic bone-marrow transplantation. We sought to further define the usefulness, yield, and sensitivity of endoscopic tissue biopsy in this patient population. A retrospective review of the clinical, endoscopic, histological, and microbiological data was obtained during the evaluation and treatment of 61 distinct episodes of unexplained gastrointestinal complaints in 37 adult allogeneic bone-marrow transplant recipients over six years at our institution. Acute gastrointestinal graft-versus-host disease was found in 12 of the 61 episodes (20%). Gastrointestinal infections were found in 14 of the 61 episodes (23%); there were Herpesvirus infections (n = 8) and fungal infections (n = 9). Patients with and without graft-versus-host disease were similar in terms of their age, sex, underlying illness, clinical symptoms and signs, physical examination, laboratory values, and endoscopic findings. Small-bowel biopsy had a sensitivity of 90% for detecting the pathological changes of acute intestinal graft-versus-host disease in this series. A high percentage of patients with gastrointestinal complaints after allogeneic bone-marrow transplantation have acute gastrointestinal graft-versus-host disease, or an opportunistic infection. Gastrointestinal graft-versus-host disease cannot be accurately diagnosed from its clinical presentation. Endoscopic small-bowel biopsy is an essential tool in evaluating this patient population.