In this study, the aim was to characterize the relationship of hypoglycemia to hepatic mitochondrial function and hepatic glycogen stores in late hemorrhagic shock. With the use of a modified Wiggers' model of hemorrhagic shock, blood glucose, hepatic mitochondrial function and hepatic glycogen were measured when reinfusion of 60 per cent of the shed blood was required to maintain the blood pressure at 30 millimeters of mercury. Defective mitochondrial energy-linked metabolism was more sensitively detected with isocitrate as substrate than with alpha-ketoglutarate, succinate or malate. The correlation between the blood and hepatic glycogen content was only 0.43 when oxidative phosphorylation was coupled. When oxidative phosphorylation with isocitrate was uncoupled, the relationship between blood glucose and hepatic glycogen was exponential, with a correlation of 0.91. The results suggest that defective energy-linked mitochondrial function impairs gluconeogenesis and that hypoglycemia occurs when oxidative phosphorylation becomes uncoupled and hepatic glycogen stores are subsequently depleted.