BODY WEIGHT REGULATION is sensitive to a number of environmental, social, and genetic pressures but is ultimately subject to a homeostatic control system linked with adiposity (23,36). This control system involves a closed-feedback loop between the central nervous system and the peripheral tissues, whereby the central nervous system interprets a complex set of signals from the periphery and subsequently sends signals to defend a certain level of body weight and fat mass. As such, there are metabolic adjustments with overfeeding and weight gain that promote weight loss (22). However, the global obesity epidemic provides evidence that the other pressures affecting body weight cannot only override these protective metabolic adjustments but can also alter the control system in a somewhat permanent fashion by gradually elevating the defended level of adiposity. In addition, there are metabolic adjustments with caloric restriction and weight loss that work to regain the lost weight (22,24,26,27). Although the other pressures affecting body weight can be used to override these metabolic adjustments, there is little evidence of an equivalent readjustment of the control system to lower its targeted adiposity level. It is this persistence of the control system and its metabolic adjustments in the face of downward fluctuations in adiposity that explain the most critical problem in obesity treatment: keeping the weight off after weight loss. It is for this reason that significant efforts have been made to increase our understanding of the metabolic drive to regain weight.One of the most fundamental metabolic adjustments in response to weight reduction is the large positive energy imbalance, or "energy gap," between intake and expenditure (26). In both humans and rodents, the drive to consume food increases and energy expenditure decreases. In order to maintain the reduced weight, the food provision must be reduced to match the suppressed level of expenditure. When this limitation on food provision is not maintained, food is ingested in gross excess of expenditure, the extra energy is stored, and weight is gained. In this issue of the American Journal of Integrative and Comparative Physiology, Evans et al. (9) report an interesting set of observations that describe this metabolic drive in two strains of rats in response to two weeks of caloric restriction. These authors have used an impressive array of metabolic monitoring tools to follow these animals prospectively through caloric restriction and the early part of the relapse to the defended body weight. Long-Evans rats responded with hyperphagia that was persistently higher than ad libitum-fed controls through 8 days of refeeding, while expenditure appeared to resolve within a few days. In contrast, the Sprague-Dawley rats had an expenditure that was still suppressed after 8 days of refeeding, while intake was higher for only the first day. The authors use this divergent response to suggest that the homeostatic response to caloric restriction may selectively target appet...