The present study was designed to elucidate the effect of FK506 on 90 min of warm ischemia of the liver and reperfusion in 30 dogs. Three groups of animals were studied. Group 1 animals received FK (0.15 mg/kg/day) for three days prior to the ischemia and group 2 animals got 2 ml of saline solution for three days instead of FK and were considered controls. In group 3 FK (0.15 mg/ kg/day) was injected immediately upon reperfusion and two days thereafter. Evaluation of the effectiveness of the drug was monitored by measuring the serum activities of AST, ALT, LDH, serum total bilirubin, malon-dialdehyde, and by histopathological examinations of the liver specimens and survival of the animals for 7 days after reperfusion. The 7 day survival of the animals in group 1 (80%) was significantly (P< 0.05) improved compared with those in group 2 (30%) and group 3 (20%). The serum activities of AST, ALT, and LDH and total bilirubin were significantly lower in group 1 than in group 2 and group 3. FK pretreatment significantly prevented hepatocellular necrosis and neutrophilic infiltration in group 1 in comparison with those in group 2 and group 3. Although the malondialdehyde level in hepatic venous blood was relatively lower in group 1, this difference was not statistically significant. Three days FK pretreatment prevented hepatocellular injury and enzyme leakage after 90 min of hepatic ischemia, whereas FK treatment immediately upon reperfusion failed to do so. In conclusion, donor organ pretreatment with FK may become a promising strategy for improved allograft survival in liver transplantation.