The conversion of fatty acids to ketones is an energy-generating process. An evaluation of its quantitative significance on the energy metabolism of the human liver is presented. It is shown that in the decompensated diabetic state ketogenesis provides most of the energy used in this organ. Thus, under these conditions, ketogenesis appears to be limited by the rate of energy utilization in the liver. Since gluconeogenesis increases the energy expenditure in the liver, gluconeogenesis can be seen to have a permissive effect on ketogenesis. It is suggested that this interaction, at the level of the energy metabolism in the liver, explains why pathological rates of ketogenesis are found in metabolic situations where gluconeogenesis is very rapid.