In the aged liver, cell proliferation and induction of DNA synthesis by epidermal growth factor is impaired. Changes in the hepatic handling of epidermal growth factor may be important for these effects. I compared epidermal growth factor handling in the livers of young and old rats. Epidermal growth factor binding capacity of plasma membranes was reduced from 1.30 f 0.15 to 0.51 2 0.19 pmollmg in young and old animals, respectively. Intracellular handling of epidermal growth factor was assessed by means of portal injection of 12SI-labeled epidermal growth factor and collection of bile samples. The extraction of epidermal growth factor showed no significant difference. After 60 min the remaining radioactivity in the aged liver was half that in young liver. The total radioactivity secreted into bile was reduced from 16.5% & 5.7% to 10.0% f 2.3% of the injected dose in young and old animals, respectively. Per gram of liver and per lo6 cpm injected, the old animals secreted only 30.9% of the amount secreted by young animals. The secretion of immunologically intact epidermal growth factor into bile was reduced from 1.6% & 0.8% to 0.78% 2 0.2% of the injected dose in the young and old animals, respectively. Perfusion experiments showed that in aged liver the amount of total radioactivity secreted into the perfusate was increased to 133.6% that of the young liver. Per gram of liver and per log cpm injected, however, we found a reduction to 80.7%.