Abstract Studies using internal jugular vein blood sampling in human subjects have demonstrated the release of noradrenaline from the brain and have provided a link between central nervous system noradrenergic neuronal activity and renal, cardiac and total body sympathetic activity. The aim of this study was to further categorise the dependence of regional sympathetic nervous function on central nervous system noradrenergic neuronal processes by combining measures of internal jugular venous noradrenaline spillover, as an indicator of brain noradrenaline release, and cerebral blood flow scans with measures of the overall integrated neuronal firing rate for the body as a whole, the spillover of noradrenaline into the coronary sinus and with measurements of resting muscle sympathetic nerve activity. Positive veno–arterial plasma noradrenaline gradients were found across the brain, with the plasma concentration being 17±3% ( p<0.01) greater in the internal jugular vein. Linear regression analysis revealed a significant relationship between the degree of muscle sympathetic nerve activity and the spillover of noradrenaline from subcortical brain regions ( y=0.1 x+16.0; r=0.81, p<0.02). The rate of spillover of noradrenaline for the body as a whole also bore a significant association with the rate of subcortical noradrenaline spillover ( y=0.01 x+2.33; r=0.71, p<0.05). Cortical noradrenaline spillover was not related to any of the sympathetic nervous system parameters measured in this study. The demonstration of a direct relationship between the rate of peroneal nerve firing and the spillover of noradrenaline from subcortical brain regions provides further support for the concept of central nervous system noradrenergic cell groups behaving in a sympathoexcitatory role.