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To evaluate the role of the liver in cortisol catabolism the extraction ratio of both cortisol and cortisone by the organs of the splanchnic area was estimated in guinea-pigs anaesthetized with pentobarbitone. The [³H]cortisol and [³H]cortisone concentrations were measured in portal and sus hepatic venous plasma during a constant infusion of [³H]cortisol or [³H]cortisone. The extraction ratio of cortisol was estimated to be 10–14% in the splanchnic area and the viscera, while in the liver it had a small negative value suggesting that the liver had produced as much or more cortisol than it had taken up. All the cortisone (95%) formed from cortisol in the viscera was eliminated from the plasma compartment by the liver. Some 75–80% of the infused cortisone was converted to cortisol; rather less of the infused cortisol was converted to cortisone (32%). Using estimates of plasma flow derived from sham-operated animals, the uptake of cortisol by the various organs was calculated. The splanchnic area extracted 41% of the infused cortisol from the plasma: 25–27% as cortisol and 13–16% as cortisone. The liver appeared to take up cortisone preferentially. The conversion of cortisone into cortisol within the liver seems to be important in limiting the amount of cortisol removed from the plasma by the splanchnic area. The liver is also important in inactivating the steroids although other sites are probably also involved.