The role of prostaglandins in the pathogenesis of the circulatory abnormalities of cirrhosis was investigated by studying the effects of prostaglandin inhibition with indomethacin (50 mg/8 h for 24 h) on the systemic and splanchnic hemodynamics in 13 patients with cirrhosis of the liver. Indomethacin administration significantly reduced cardiac output (from 7.44 +/- 0.7 to 6.78 +/- 0.7 L/min, p less than 0.05) and increased peripheral vascular resistance (from 990 +/- 104 to 1155 +/- 140 dyn X s X cm-5, p less than 0.05). Arterial pressure was not modified. These changes in systemic hemodynamics were associated with a significant reduction in hepatic blood flow (from 1.88 +/- 0.43 to 1.48 +/- 0.3 L/min, p less than 0.05) and with a slight decrease of portal pressure (from 18.8 +/- 1.3 to 17.5 +/- 1.4 mmHg, p less than 0.05). These results suggest that endogenous prostaglandins contribute to the increased cardiac output and diminished vascular resistance observed in cirrhosis of the liver. In addition, by promoting splanchnic vasodilation, prostaglandins may contribute to increased portal pressure in these patients.