Peptic ulcer bleeding is a frequent cause of upper G-I bleeding. Endoscopic injection therapy with hypertonic saline-epinephrine (HS-E) is a cost-effective and widely used therapy for hemostasis; however, 1∼3% of patients experience bleeding or perforation. A 70 year-old male patient was admitted with melena and hematemesis. An endoscopy on admission showed the presence of a 1 cm- sized well-demarcated ulcer with pulsatile bleeding at the lesser curvature of the distal antrum. Approximately 28 mL of HS-E solution was injected around the exposed vessel. Follow-up endoscopy performed 7 days later showed the presence of a 2 cm-sized newly developed mucosa necrosis at the lesser curvature of the pyloric channel, which was caused by ischemic necrosis of the gastric mucosa after HS-E injection. Endoscopic injection therapy with HS-E solution is a relatively safe technique, but mucosa necrosis can occur with the use of a dose of HS-E that is considered safe. We report a case of gastric mucosa necrosis following endoscopic HS-E injection therapy of a bleeding peptic ulcer. (Korean J Gastrointest Endosc 2008;37:20-24)