The effect of liver support on the adenylate energy charge (ATP + 1/2 ADP) / (ATP + ADP + AMP) of the remnant liver after major hepatic resection was studied in rabbits. The present study emphasizes the principle of the use of homologous or heterologous liver for preventing the decrease in the energy charge of the remnant liver after major hepatic resection. The energy charge level provides the cell with a very sensitive intracellular control mechanism. Regulatory enzymes from biosynthetic sequences exhibit very little activity at low levels of energy charge, and their activities increase sharply at high charge values. The energy charge level of the remnant liver maximally decreased from the normal level of 0.843 to 0.767 at 24 hours after 70% hepatectomy. The energy charge level increased from 0.767 to 0.828 after one hour of cross-circulation of systemic blood between the 24-hour, 70% hepatectomized rabbit and a normal rabbit. An increase from 0.767 to 0.801 also occurred after one hour of charcoal hemoperfusion. Although either means of liver support serves to restore energy charge levels, the above results suggest that cross-circulation may be more effective than charcoal hemoperfusion for biosynthesis in the regenerative processes of the remnant liver.