Hepatocytes were isolated from rats following bilateral nephrectomy, Ureter ligation or sham Operation under sodium pentobarbital (Nembutal®) anesthesia to investigate the potential role of energy Charge and redox State for the gluconeogenetic ability of liver cells. Ketogenesis from /-serine, sodium pyruvate or dihydroxyacetone was significantly higher in hepatocytes of aeutely uremic rats indicating higher concentration of reducing equivalents in the mitochondria. During ineubation, the mitochondrial redox State characterized by β-hydroxybutyrate/acetoace-tate ratio moved into direction of reduetion in all experimental groups, whereas cytosolic redox State characterized by lactate/pyruvate ratio shifted to the oxidative State indicating lack of cytosolic reducing equivalents. Hepatocyte ATP and oxoglutarate production of ureter-ligated rats were significantly higher compared with binephrectomized or sham-operated animals independent of the Substrates used. Simultaneously, energy Charge showed values higher than 0.85 only in hepatocytes of ureter-ligated animals indicating high energy supply for energy requiring processes. We conclude that hepatic gluconeogenesis and ketogenesis of aeutely uremic rats are limited by a lack of cytosolic reducing equivalents independent of cell energy supply.