A 44 year old-healthy female presented chronic and stable high levels of plasma noradrenaline (NA) without any major change in adrenaline. The diagnosis of phaeochromocytoma was discarded. These increased levels of NA offered an unique opportunity to investigate under in vivo conditions a putative regulation of alpha-adrenoceptors by this endogenous catecholamine. Infusion rates of exogenous NA up to 0.74 micrograms/kg per min were unable to induce any change in blood pressure (or heart rate) in the subject, In contrast, in normotensive controls, an increase in blood pressure (+ 15 mm Hg) was observed with 0.39 micrograms/kg per min. The magnitude of yohimbine-induced increase in plasma NA was similar in the subject and in the controls. Platelet alpha 2-adrenoceptors evaluated by specific [3H]-yohimbine binding showed a significantly lower level in the subject when compared to controls. The results show that a sustained increase in plasma NA is able to induce down-regulation of alpha-adrenoceptors. This down-regulation can explain the lack of arterial hypertension despite the increased sympathetic tone.