In cirrhotic livers, the intrahepatic resistance is increased and drug elimination and portal transhepatic flow are decreased. The aim of our work was to study the effect of a twofold increase in portal blood flow during 2 hr on the hemodynamic parameters, drug elimination and hepatic viability in eight isolated perfused human cirrhotic livers. Using an oxygenated recirculating system with independent arterial and portal flows, we perfused livers with Kreb's buffer bicarbonate solution, bovine serum albumin (20 gm·L−1) and human red blood cells (hematocrit 20). The flow was maintained at a basal level of 0.713 ± 0.19 L/min for 1 hr and then increased and maintained for 2 hr at twice the basal flow. Portal pressure-portal flow curve slopes were linear (27.04 ± 21.06 mm Hg·L−1·min; range = 6.43 to 60.8) and correlated with intrahepatic resistance during the basal-flow period (r = 0.87, p < 0.01). Parameters registered during the basal- and high-flow periods were compared by use of Student's t test: portal pressure increased from 23.5 ± 7 to 37.3 ± 16.7 mm Hg (p < 0.05); arterial pressure increased from 80.3 ± 19 to 103.5 ± 26 mm Hg (p < 0.005); hepatic artery flow resistance increased 31.9 (from 690.1 ± 218 to 899.4 ± 269 mm Hg·L−1·min; p < 0.005); indocyanine green clearance increased by 28.2 (from 86.0 ± 58.3 to 109.2 ± 74.8 ml·min−1·kg liver−1; p < 0.04). No significant differences were observed in enzyme release, biliary flow (n = 5) and oxygen consumption. Histological examinations demonstrated sinusoidal dilatations in six of eight cases. These results suggest that better liver perfusion and function of cirrhotic nodules might be obtained by increasing portal flow and perfusion pressure. (Hepatology 1994;19:375–380).