Evidence indicates that hypothalamic norepinephrine (NE), acting via alpha 2-noradrenergic receptors, and also circulating glucose both have an important role in the control of normal feeding behavior in rats. In this report, we studied the relationship between glucose and the alpha 2-noradrenergic system, by manipulating blood glucose levels and analyzing changes in the binding of [3H]p-aminoclonidine [( 3H]PAC) to alpha 2-noradrenergic receptors in discrete hypothalamic areas. Brief periods (1-3 hr) of food deprivation, at the onset of the dark cycle, produced a significant decline in serum glucose levels and a simultaneous decrease in alpha 2-receptor binding sites, specifically in the hypothalamic paraventricular nucleus (PVN) as opposed to other hypothalamic areas. Restoration of circulating glucose levels, by refeeding for 0.5 hr after 2.5 hr food deprivation or by administration of glucose to 1 hr food-deprived rats, prevented this decline in serum glucose, as well as the reduction in PVN alpha 2-noradrenergic receptor density. In each of these experiments, a strong positive correlation between circulating glucose levels and PVN alpha 2-noradrenergic receptor sites was obtained. These findings suggest that blood glucose has direct impact upon alpha 2-noradrenergic receptor activity in the PVN and may affect feeding behavior, in part, through this neurochemical system.