Using hepatic vein catheterization this study has provided the first direct measurement of morphine hepatic extraction in 8 controls and 8 cirrhotics. The extraction ratio was 0.52 in the control group and was reduced by 25% in the cirrhotics. This reduction is due to impaired enzyme capacity rather than reduced blood flow. The effect of cirrhosis is less than that reported in similar studies of high clearance oxidized drugs and this lends support to the concept that glucuronidation may be relatively spared in cirrhosis. A discrepancy between the systemic clearance and the hepatic clearance provides indirect support for extra-hepatic metabolism of morphine.