Rats with ventromedial hypothalamic lesions (VMH) have increased ability to accumulate energy. The aim of this investigation was to characterize the main processes responsible for the reduced energy expenditure, using indirect calorimetry, nitrogen, and energy balance techniques. Metabolism was studied during different metabolic conditions created by a strict feeding regimen with concentrated feeding periods. A computerized system for indirect calorimetry enabled continuous study of individual animals for prolonged time periods. We found a mean decrease of 15.5% in total energy expenditure and decreased nitrogen retention in VMH rats. Calculation of respiratory quotient (RQ), energy expenditure, and the metabolic mixture demonstrated fluctuations in metabolism in accordance with the feeding regimen. The same percent reduction in resting postabsorptive energy expenditure was found as in total expenditure. Quantitatively, this main finding means that metabolic processes that occurred both in the resting and postabsorptive state were responsible for two-thirds of the total reduction in energy expenditure, whereas only one-third could be attributed to differences in dietary-induced thermogenesis and/or physical activity. It is concluded that VMH-animals spent as much as 10.3% of their total energy expenditure on liponeogenesis compared with 2.5% in controls.