It has previously been established that norepinephrine (NE) in the central nervous system is involved in feeding and the development of obesity. The present experiments were carried out to investigate the relationship between the uptake of NE by a crude hypothalamic homogenate and NE-mediated sympathetic activity in interscapular brown adipose tissue (IBAT). Sympathetic nervous system activity was assessed by measuring the binding of the purine nucleotide guanosine-5'-diphosphate (GDP) to mitochondria isolated from IBAT. Four situations known to alter food intake and sympathetic activity, namely, corticotropin releasing factor infusion, adrenalectomy, fenfluramine treatment and obesity due to genetic transmission were studied. In each case, [3H]NE uptake by the hypothalamic preparation and GDP binding to IBAT mitochondria were measured. A highly significant negative correlation between the uptake of NE by hypothalamic homogenates and the binding of GDP to IBAT mitochondria was obtained in both lean and obese animals. These findings are discussed with regard to the regulation of food intake and sympathetic nervous system mediated thermogenesis.