1 The effects of guanethidine pretreatment on the release of [14C]-histamine during the reflex vasodilatation induced in the atropinized gracilis muscle by rapid intravenous administration of noradrenaline, were studied in dogs. 2 After guanethidine treatment the haemodynamic reflex response was completely abolished and no appreciable modification of [14C]-histamine release from the gracilis muscle following intravenous noradrenaline was observed. 3 These results suggest the hypothesis that the withdrawal of the sympathetic discharge represents the mechanism of histamine release during the reflex vasodilatation. Therefore, guanethidine would suppress both the passive and the histaminergic component of the baroreceptor reflex through the abolition of the sympathetic tone.