This study was designed to investigate the effects of 17 beta-estradiol benzoate (E(2)B) on brain glucose uptake and transport across the blood-brain barrier (BBB), Both a time- and dose-response evaluation of the effect of E(2)B on glucose uptake in the central nervous system (CNS) were conducted, E(2)B, in doses ranging from 1 to 100 mu g/kg body weight, was injected subcutaneously at 2 to 24 h prior to evaluation, The 4-h time point and 10 mu g/kg dose of E(2)B produced the most widespread increases in glucose uptake, Six regions responded to E(2)B with elevated glucose uptake by as much as 120% when compared to oil-treated controls, We then evaluated the effects of E(2)B on transport of glucose across the BBB, E(2)B significantly increased the extraction of labeled sugar across the BBB by 40% without affecting extraction of the internal standard. Collectively, these studies indicate that physiological levels of estradiol (E(2)) may play an important role in modulating cerebral glucose homeostasis.