Factors related to the prognosis of patients with hyperbilirubinemia were investigated in 16 highly jaundiced patients. Patients who died within 3 weeks showed a deterioration of the hepatic energy status, measured by the arterial ketone body ratio, but patients who did not die within 3 weeks after the measurement of the ketone body ratio had a ratio within the normal range, despite high total bilirubin levels (18 mg/0.1 L). C3, C4 and CH50 in the former were also significantly lower than those in the latter. However, endotoxin and high fever occurred to the same extent, in the both groups. Thus, hepatic energy balance is the most pertinent factor related to prognosis, and is concerned with both the hepatocyte and reticuloendothelial systems. On the other hand, infection or endotoxin, when the energy balance is disturbed, becomes an aggravating but not a fundamental factor.