1. Hepatic metabolism of renin activity was studied in seven normal dogs, twelve dogs with acute hepatic allograft rejection, five dogs with chronic toxic hepatitis and in seven isolated canine liver preparations.
2. Renin activity was measured by radioimmunoassay in hepatic arterial, portal venous, and hepatic venous plasma (PRA), in bile (BRA) and in perfusate (PsRA).
3. There was a significant gradient of PRA across the normal liver (P < 0.03) and of PsRA across the isolated liver (P < 0.05).
4. There was no significant PRA gradient across the liver of dogs with allograft rejection (acute hepatic necrosis).
5. Dogs with chronic toxic hepatitis showed decreased fractional extraction of PRA but otherwise their data were normal.
6. There was a significant difference between portal venous PRA (8.69 ±1.51 ng ml−1h−1) and hepatic arterial PRA (5.67±1.91 ng ml−1h−1) (P < 0.05).
7. BRA accounted for only 0.04% of hepatic extraction of PRA, suggesting that more important mechanisms for hepatic renin metabolism are binding or destruction of renin by the hepatic tissue.