The effects of two vasodilators, papaverine and pentoxifylline (a methylxanthine derivative), on liver function after 19 hr hypothermic preservation were investigated. Hypothermic preservation was performed according to the standard technique, and liver hemodynamics and function were studied during 70 min immediately after reperfusion in an isolated perfused rat liver system. No significant changes occurred after hypothermic storage for 5 hr. However, when the storage was prolonged to 19 hr, bile flow and taurocholate intrinsic clearance were significantly reduced; transaminase release was markedly increased and histological studies demonstrated centrilobular necrosis. Concomitantly, liver blood flow was significantly reduced and intrahepatic vascular resistance was increased. Papaverine and pentoxifylline administered during preservation and at the time of reperfusion significantly improved all parameters. The improvement was more pronounced after pentoxifylline, and this group showed no significant difference in any of the studied parameters from the control livers. The results show that two vasodilators significantly protect the liver during long hypothermic preservation. The data suggest that abnormalities of liver microcirculation are of major importance in the pathogenesis of liver injury after hypothermic storage.