Introduction: There is increasing evidence that brown adipose tissue (BAT) has an important physiological role beyond that of thermoregulation in newborn infants and rodents (1-3). Adult humans thus have significant amounts of BAT (4-6) and as a highly metabolic tissue with the capacity to oxidise both glucose and lipid, attention has turned to its involvement in the pathogenesis of obesity (7). Central regulation of BAT is through the adrenoreceptor activated cAMP pathway and the liberation of free-fatty acids (FFA), which are acute metabolic substrates for the BAT specific uncoupling protein (UCP1). Rapid activation of UCP1 at birth is mediated in part by the prepartum surge in cortisol (8), but whether excess cortisol administration may potentiate sympathetic nervous system (SNS) induced BAT thermogenesis is unknown. This was the first in vivo study to examine the effects of acute hypercortisolemia on BAT function in healthy human subjects, assessed by thermal imaging. Methods: Eight healthy male volunteers (age 20 y, weight 75 kg, BMI 23.0 kg×m2) participated in this randomised, double-blind, placebo controlled study. Thermal imaging of the supraclavicular neck region (SCR) was conducted prior to and post a standardised calorie-controlled meal, proceeded by a 14hr constant infusion of hydrocortisone (HC; 0.2 mg.kg-1.h-1) or saline (S). The following morning, isoprenaline (ISO; 25 ng.kg fat-free mass-1.min-1) was infused for 1hr. BAT thermogenic activity was measured at baseline and throughout the infusion. Blood samples were drawn throughout and analyzed for cortisol, glucose, triglycerides, and FFA. Results: HC significantly increased plasma cortisol concentrations (AUC 143±16 vs 2358±290 nmol/L, p<0.001) and basal NEFA (AUC 1073±98 µmol/L; p=0.027 compared to control). At thermoneutrality, acute hypercortisolaemia increased basal SCR (35.92 vs 35.49°C, p=0.004). ISO increased NEFA both under control conditions (AUC 1549±173 µmol/L; p=0.001 compared to basal) and during HC (AUC 2039±194 µmol/L; p=0.001). HC did not have any effect on the magnitude of plasma NEFA increase in response to ISO (Δ AUC 953±155 vs 979±175 µmol/L). Plasma glucose concentrations did not change during ISO infusion. ß-adrenergic stimulation resulted in a highly localized increase in SCR temperature (0.68±0.18°C, p=0.001) representative of BAT thermogenic activity, both under control and hypercortisolaemia conditions (0.52±0.14°C, p=0.001). Conclusions: GCs can modulate human BAT activation by the induction of ß-AR-induced lipolysis and provide a novel insight into the potential role of BAT in targeting obesity and cushing’s syndrome disorders.