The effects of sustained changes in sympathetic activity, produced by intracisternal (i.c.) infusion of yohimbine or clonidine, on the formation of the intraneuronal noradrenaline metabolite, dihydroxyphenylglycol (DHPG), and on the efficiency of noradrenaline reuptake were examined in conscious rabbits. Noradrenaline spillover was estimated by radiotracer dilution analysis of i.v. infused [3H]noradrenaline. Noradrenaline reuptake was estimated from the amount of DHPG derived from recaptured neurotransmitter and the effects of desipramine-induced neuronal uptake blockade on noradrenaline clearance and plasma [3H]DHPG. The efficiency of neuronal reuptake was assessed from relationships between noradrenaline reuptake and spillover. Sustained sympathetic activation with i.c. yohimbine increased the amount of plasma DHPG that was derived from recaptured noradrenaline as well as that derived from other sources. Acute administration of desipramine decreased both components so that the decrease in plasma DHPG overestimated the amount derived from recaptured noradrenaline. Thus, estimation of the component of plasma DHPG that was derived from recaptured noradrenaline was most accurately achieved by examination of relationships between plasma noradrenaline and DHPG. Noradrenaline reuptake and spillover into plasma were decreased by i.c. infusion of clonidine and increased by i.c. infusion of yohimbine. Neither i.c. infusion of clonidine nor yohimbine altered relationships between noradrenaline reuptake and spillover indicating that the efficiency of neuronal reuptake was unaltered by sustained changes in sympathetic activity.