Standard therapy for variceal bleeding includes endoscopic sclerotherapy and esophageal balloon tamponade. In addition, pharmacologic therapies, including arginine vasopressin (AVP), are frequently used in hemodynamically unstable patients or where sclerotherapy has been unsuccessful. A case is described herein of a 30-year-old woman with a history of ethanol abuse, hematemeisis, and biopsy-proven hepatic cirrhosis in which the addition of AVP to an antivariceal regimen of octreotide was associated with a paradoxical episode of hypotension, bradycardia, and hypoxia. Indeed, within 15 minutes after initiation of an AVP infusion, the patient exhibited hypotension with a systolic blood pressure of 80 mmHg, a relative bradycardia to 76 beats per minute, and a desaturation of blood oxygen to 84%. The AVP infusion was discontinued 2 hours later and blood pressure, heart rate, and oxygen saturation rapidly returned to baseline. This temporal correlation between the onset and termination of the physiologic effects and the initiation and discontinuation of the AVP infusion suggests a causal relationship. The paradoxical physiologic effects might reflect cardiac ischemia secondary to vasospasm and/or central suppression of the autonomic nervous system induced by AVP.