The present study was undertaken to determine the effect of infusion of adenosine triphosphate-magnesium chloride (ATP-MgCl2) after 60 or 90 minutes of total hepatic ischemia, since previous work had shown a protective effect of the administration of this complex in postischemic acute renal failure and shock. Following the release of the hepatic vascular occlusion, ATP-MgCl2, ATP alone, or MgCl2 alone (0.25 ml, 12.5 μmoles each) was given intravenously to treated animals, and saline (0.25 ml) was given to the controls. Survival was measured over a period of 5 days. The survival rate after 60 and 90 minutes of ischemia was 87.5% and 69.2% in the ATP-MgCl2-treated animals, 43.8% and 23.1% in the control group, respectively. When either ATP or MgCl2 alone was given after 60 minutes of hepatic ischemia, the survival rate was 20% and 30%, respectively. In another group of animals, serum enzymes and hepatic ATP levels were measured 1 hour following the release of 60 minutes of ischemia. Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were greatly increased following ischemia, and the levels of these enzymes were significantly lowered with ATP-MgCl2 treatment. Hepatic cellular ATP levels and energy charge were significantly decreased during occlusion; however, ATP levels were increased and the energy charge returned to normal following ATP-MgCl2 treatment. Thus increased survival and improved hepatic function after ischemia was associated with elevated cellular ATP levels following ATP-MgCl2 administration. While the precise mechanism of action of ATP-MgCl2 remains unknown, these observations may have important implications for future use in organ preservation, management of postischemic acute hepatic failure, and multiple systems failure.