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A 44-year-old man with hepatitis C-associated liver cirrhosis, cyanosis, digital clubbing, and platypnea presented with left-side hemiplegia found to be due to a brain abscess. Hepatopulmonary syndrome was diagnosed after demonstration of the presence of a massive intrapulmonary shunt. Although the anomalous vascular channel never was defined anatomically, follow-up studies confirmed the presence of a functional shunt. Culture of a sample from the abscess yielded Streptococcus intermedius. It was hypothesized that the patient's pulmonary vascular pathology was due, in large part, to chronic elevated levels of nitric oxide (a potent vasodilator thought to be generated by endotoxin absorbed from the gut). Treatment with oral norfloxacin was initiated on the basis of data that this antibiotic reduces endotoxemia and concomitant nitric oxide production in patients with cirrhosis. Four months after initiation of treatment, the patient's hypoxia had resolved.