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In order to elucidate the mechanisms by which beta-adrenoceptor blockade leads to a reduction in portal pressure, we have measured portal pressure, heart rate and cardiac index in 17 patients with cirrhosis and portal hypertension following the oral administration of the selective beta 2-adrenoceptor blocking agent, ICI 118551, in the two dosage ranges 10-20 mg and 50-100 mg. There was a fall in portal pressure in 14 of the 17 patients from a median of 17 mm Hg to a median of 15 mm Hg, P less than 0.01, that occurred only at 60 min following administration of the drug. Although there were early systemic haemodynamic changes, with a significant fall in heart rate and cardiac index from before to 30 min after the ingestion of ICI 118551 (median heart rates 86 and 80 beats/min respectively, P less than 0.01, median cardiac indices 3.5 and 3.31 min-1 m-2, P less than 0.05), these occurred before the fall in portal pressure and were unrelated to changes in portal pressure. This reduction in portal pressure independent of systemic haemodynamic changes is consistent with beta 2- adrenoceptor blockade within the splanchnic and hepatic arterial circulations; subsequent increases in splanchnic and hepatic arterial resistances with a concomitant fall in portal blood flow and hepatic portal resistance may lead to the reduction in portal pressure.