We retrospectively studied 22 patients with hepatopulmonary syndrome (HPS) evaluated at the Mayo Medical Center from 1984 to 1991. All patients had hepatic cirrhosis with clinical evidence of portal hypertension; 13 (59 percent) had severe hypoxemia while breathing room air in the supine position (PaO2 < 60 mm Hg), and 14 of 16 (88 percent) had orthodeoxia breathing room air. On the basis of angiographic observations, we defined type 1 and type 2 patterns of pulmonary vascular abnormalities in HPS. Response to 100 percent oxygen and therapeutic regimens may differ in the angiographic patterns. Substantial deterioration in PaO2 associated with clinically stable hepatic dysfunction was documented in five of seven patients studied with sequential arterial blood gas testing; four subsequently died within 48 months. Overall mortality was 41 percent, occurring a mean of 2.5 years after diagnosis. In 7 of the 22 patients, we prospectively studied the effect of somatostatin analogue given subcutaneously for 4 consecutive days. No significant improvement in PaO2 was documented while breathing room air or 100 percent oxygen (p < 0.05). We conclude that in selected patients with clinically stable hepatic dysfunction and deteriorating oxygenation, the prognosis is poor. Our data in combination with recent surgical reports suggest that liver transplantation may be the treatment of choice in patients with HPS and worsening oxygenation.