The binding and efflux characteristics of [14C]‐guanethidine and [3H]‐noradrenaline were studied in heart slices from rats which were pretreated with reserpine and nialamide. Binding of both compounds occurred at extra‐vesicular sites within the adrenergic neurone. After a brief period of rapid washout, the efflux of [14C]‐guanethidine and [3H]‐noradrenaline proceeded at a steady rate. The efflux of both compounds appeared to occur from a single intraneuronal compartment. (+)‐Amphetamine accelerated the efflux of [14C]‐guanethidine and [3H]‐noradrenaline; this effect was inhibited by desipramine. Unlabelled guanethidine and amantadine also increased the efflux of labelled compounds. Cocaine in high concentrations increased slightly the efflux of [14C]‐guanethidine but not that of [3H]‐noradrenaline. Heart slices labelled with [3H]‐noradrenaline became refractory to successive exposures to releasing agents although an appreciable amount of labelled compound was still present in the slices. It is suggested that [14C]‐guanethidine and [3H]‐noradrenaline are bound at a common extra‐vesicular site within the adrenergic neurone. Binding of guanethidine to the extra‐vesicular site may be relevant to its pharmacological action, i.e., the blockade of adrenergic transmission.