Isolated perfused livers from rats fasted 16 h before surgery showed a strong decrease in oxygen consumption as well as hepatotoxic responses when subjected to 30 min of hypoxia (95%, N2/5% CO2) followed by 90 min of reoxygenation (95% O2/5% CO2). Toxicity was evident by a release of enzymes (LDH, GPT, GLDH) into the perfusate and by a nearly complete suppression of bile flow. Hepatic reduced gluthathione dropped to about 20% and hepatic ATP to about 50% of the initial values. Furthermore, the concentrations of thiobarbituric acid reactive (TBA) material increased eightfold in the perfusate and by 70% of the control values in the livers. Glycine added to the perfusate at concentrations of 3, 6 and 12 mmol/l prevented dose-dependently all measures of hepatotoxicity as well as the indices of lipid peroxidation induced by hypoxia/reoxygenation. A maximal and nearly complete protection was obtained with 12 mmol/l glycine. Glycine increased the bile flow of perfused livers not subjected to hypoxia and attenuated the drop of bile flow induced by hypoxia-reoxygenation. Ligation of the bile duct, however, did not influence the cytoprotective effects of glycine in hypoxia-reoxygenation induced hepatic injury. In conclusion, glycine is an effective antidote against hypoxia-regoxygenation induced injury of the isolated rat liver.