In 5% of patients with gastrointestinal bleeding, standard evaluation fails to reveal the source of the bleeding. We describe the management of 71 patients treated for obscure gastrointestinal bleeding at the Mount Sinai Medical Center, New York, New York, from 1985 to 1991. There were 38 men (54%) and 33 women (46%). The mean age was 60 years. The patients had bleeding episodes for a mean period of 26 months and required an average of 20 units of blood prior to surgical treatment. All had undergone an extensive diagnostic workup including barium contrast studies, endoscopies, and angiographies. Some had multiple bleeding scans, Meckel scans, and surgical explorations. Three patients were found to have "watermelon stomach" on endoscopy and had an antrectomy. Sixty-eight (96%) patients underwent a preoperative small bowel enteroscopy, which revealed the precise diagnosis in 50 (70%) of the patients. All patients underwent surgery. In 30 (42%) patients in whom the bleeding site was not apparent at exploration, intraoperative enteroscopy was performed. Two actively bleeding patients had intraoperative enteroscopy, which failed to localize the bleeding site, and intraoperative scintigraphy was utilized. The bleeding was found to originate in small bowel arteriovenous malformation (AVM) (28 patients), leiomyoma (8 patients), primary small bowel malignancies (11 patients), and other causes (24 patients). Fifty-six patients (80%) had no further bleeding; 9 with multiple small bowel AVM have experienced rebleeding and are alive. Six patients died of recurrent bleeding, and six died of metastatic cancer. An aggressive approach should be applied in patients in whom standard evaluation fails to localize the source of gastrointestinal bleeding. Enteroscopy, surgical exploration with additional intraoperative enteroscopy, and occasional intraoperative scintigraphy can achieve an excellent yield and allow resection and potential cure.