We encountered 2 patients who underwent esophagogastroduodenoscopy for epigastric abdominal pain, which showed gastric mucosal erosions covered with adherent exudate. Microscopic examination of biopsies from the lesions obtained from the 2 cases revealed characteristic pathologic abnormalities that shared striking similarities. These included superficial mucosal necrosis and capillary vascular degenerative change in a background of reactive or chemical gastropathy. Further review of records identified ongoing oral doxycycline use in both patients. After cessation of the drug both patients' symptoms resolved. A follow-up esophagogastroduodenoscopy in 1 patient showed normal gastric mucosa. This pattern of injury had not been previously described and seems to be characteristic for doxycycline-induced gastric mucosal toxicity. Recognition of the clinical, endoscopic, and pathologic features described here may facilitate prompt diagnosis and management of this condition.