Genetically obese animals have been shown to have a reduced number and affinity of glucocorticoid receptors. The relationship between the alterations in receptor binding and the regulation of energy balance is not known. We sought to determine the role of body energy/feeding status on the binding characteristics of glucocorticoid receptors. To accomplish this, we examined the effect of long-term food restriction on the number and affinity of hepatic glucocorticoid receptors from Sprague-Dawley rats. After 3 weeks of food restriction (40% of ad lib), animals were bilaterally adrenalectomized. Livers were removed, a crude cytosolic glucocorticoid receptor fraction was isolated, and radioreceptor assays were performed. Glucocorticoid receptors from food-restricted rats showed a significant reduction in the dissociation constant (Kd) as compared to receptors derived from free-feeding controls. No difference in receptor number was observed. These results suggest that energy or feeding status of the animal may influence the affinity of hepatic glucocorticoid receptors, while receptor number may be independent of this status.