Reduced energy expenditure associated with reduced energy intake has been used as an explanation for resistance to weight loss in obese patients. Decreases in serum T3 concentrations and body cell mass induced by restriction of energy intake may contribute to the reduced energy needs. In the present study, mean resting metabolic rate (RMR) was reduced by 9.4% after 5 weeks of a very low energy diet (472 Cal/day) in six obese women, and the mean serum T3 concentration decreased 46%. However, the lowest RMR values measured were similar in these subjects (mean, 1328 Cal/day; range, 1110-1578 Cal/day) to RMR values of lean women (n = 19; mean, 1241 Cal/day; range, 938-1450 Cal/day) and moderately overweight women ingesting ad libitum diets (n = 8; mean, 1335 Cal/day; range, 1064-1533). Decreases in total body potassium (10%) and 24-h urinary creatinine excretion (23%) suggested that there was a substantial loss of body cell mass during weight loss, whereas nitrogen balance suggested that changes in body cell mass were slight. These data and those of previous studies indicate that even after rapid weight loss, the resting energy requirements of obese or previously obese subjects are not abnormally low relative to those of nonobese subjects, even though the concentrations of T3, a major thermogenic hormone, are substantially reduced. The hypometabolic response to weight loss cannot explain the failure of obese subjects to lose weight on weight-reducing regimens.