Tyramine-dependent depletion of norepinephrine was shown to occur from a single kinetically defined compartment. The kinetics of depletion were related to the tyramine concentration and were independent of the amount of norepinephrine within the neuron. Tyramine depleted equivalent amounts of norepinephrine from cytoplasmic, biosynthetic, stable and labile intraneuronal storage compartments by a cocaine-sensitive process. The norepinephrine specific activity of the thoracic aorta remained constant even after greater than 80% depletion due·tyramine. The results show no evidence for a tyramine-resistant pool(s) of norepinephrine vithin adrenergic neurons.