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Although transmission at postganglionic adrenergic nerve endings can be blocked by a wide variety of guanidine derivatives (Mull,

(-)-,f-Hydroxyphenethylguanidine is the most active of a series of aralkylguanidines studied for their ability to lower the noradrenaline content of sympathetically-innervated tissues. It is several times more potent in this respect than guanethidine, but, unlike guanethidine, it produces only weak impairment of sympathetic transmission. In this paper we have compared the mechanisms of noradrenaline depletion by guanethidine and (-)-,8-hydroxyphenethylguanidine, and studied the relationship between noradrenaline depletion and sympathetic blockade. The nature of the adrenergic neurone blocking action of guanethidine is discussed in the light of these results. METHODS