In order to reassess the role of duodenal ulcers as a cause of acute upper gastrointestinal hemorrhage in patients with chronic renal failure, 20 consecutive patients with moderate to severe chronic renal failure and a comparison group of patients without renal disease who were seen for acute upper gastrointestinal hemorrhage were reviewed. Gastric bleeding sites (gastric ulcer in 35 percent and gastritis in 20 percent) rather than duodenal ulcers were the most common sources of bleeding and were significantly associated with the use of ulcerogenic drugs. Patients with renal disease in whom acute upper gastrointestinal hemorrhage developed had significantly more morbidity and a trend toward higher mortality than the comparison group of patients without renal disease. It is concluded that gastric mucosal lesions, at least in part due to the use of ulcerogenic drugs, are the most common cause of significant acute upper gastrointestinal hemorrhage in patients with chronic renal failure.