A 72-year-old woman presented to the emergency department with epistaxis and generalized telangiectasia. The patient was known to have Rendu-Osler-Weber syndrome, or hereditary hemorrhagic telangiectasia, an autosomal dominant disorder that is associated with arteriovenous fistulae of many organs. She had had previous episodes of epistaxis and GI tract bleeding. Drs K. Rauhilla, Mamta Verma, and Sonia Arunabh of Flushing, NY, write that the clinical triad of multiple telangiectasias, recurrent hemorrhages, and familial occurrence characterizes Rendu-Osler-Weber syndrome. In about 80% of affected patients, frequent nosebleeds are the initial manifestation of the disorder. The characteristic dark red, usually elevated lesions that typically appear in adulthood are arteriovenous malformations of the dermal microvasculature. Most commonly, these lesions arise on mucous membranes (A), face, distal extremities (B), and beneath the nails. The gut, brain, and lungs also may be affected. The degree of systemic involvement varies; recurrent epistaxis and episodes of lower GI tract bleeding, which affected this patient, are most common. As many as 20% to 30% of persons with this disease have pulmonary arteriovenous malformations that may manifest as dyspnea from a right-to-left shunt, severe clubbing, and cyanosis (C). Bleeding can lead to hemoptysis and hemothorax. Nervous system complications, such as stroke and brain abscess, may arise from paradoxical emboli. Arteriovenous malformations in the brain can cause subarachnoid hemorrhage and epilepsy. In patients with suspected Rendu-Osler-Weber syndrome, examine all mucosal surfaces for lesions. Spiral CT scanning is the preferred study for detecting lesions in the chest and the brain. Endoscopy and angiography can demonstrate arteriovenous malformations of the GI tract. Angiographic embolization with metal coils, which can be repeated easily if necessary, has become the mainstay of therapy for lung or brain lesions. Balloon occlusion and surgical excision are more invasive therapeutic options. Nasal and GI tract arteriovenous malformations can be treated with laser photocoagulation, electrocautery, or embolization.