The mechanism of the elevation of serum y glutamyl transpeptidase(y GTP) activity in chronic hepatic injury is still not clear. The authors investigated serum and hepatic tissue y GTP activities by biochemical and enzyme histochemical methods on the experimentally in- duced extrahepatic cholestasis and hepatic septal fibrosis in rat. The animals with chronic extrahepatic cholestasis induced by ligation of comrnon bile duct were sacrificed at every 1 week for 4 weeks. The animals with septal fibrosis induced by biweekly intraperitoneal injec- tion of swine serum were sacrificed at every 2 weeks for 12 weeks. The serum y GTP activity of both groups of animal was investigated by biochemical method and the obtained data were analyzed statistically. The livers of both animal groups were examined histopathologically and histochemically. In animals with extrahepatic cholestasis, the activities of serum y GTP, AST, and ALT were elevated significantly than those of control. The elevation of serum enzyrne activity was more marked in y GTP than others. In animals with hepatic septal fibrosis, serum y GTP activity was slightly elevated than that of control but statistically not significant. The activities of serum AST and ALT were significantly elevated than those of control. The re- markable histological finding in the liver with ligation of common bile duct was marked prolif- eration of intrahepatic bile duct extending through hepatic lobules with time. The noticeable finding in the liver with administration of swine serum was septal fibrosis progressing more markedly and more frequently with time trend. In the animals with ligation of common bile duct or administration of swine serum, tissue y GTP activity in the liver was detected pre- dominantly in epithelium of the bile ducts and lightly in the hepatocytes located in periportal areas. On the basis of above findings it is suggested that elevation of serum y GTP activity is of biliary cell origin and not caused by hepatocyte induction, and that the induced y GTP from biliary cells flows backward into sinusoidal blood.(Korean J Gastroenterol 1994; 26: 816 824)