Adrenergic neuron blockade produced in rabbit aortic strips by bretylium and bethanidine has been studied. Differences were noted in the characteristics of approximately equal, strong neuron blockade produced by these two chemically different agents. The blockade produced by bretylium was readily reversed by washout of the drug from the tissue bath whereas blockade produced by bethanidine was slowly reversed. Desmethylimipramine accelerated the recovery after the washout of bretylium, but had little effect in accelerating recovery following the washout of bethanidine. Desmethylimipramine prevented the onset of blockade from bretylium whereas it only delayed the onset of blockade from bethanidine. Desmethylimipramine also completely antagonized an established blockade due to bretylium but only slightly antagonized an established blockade due to bethanidine. It is suggested that the differences observed between these two neuron blocking agents are the result of their differential retention inside the neuron: bretylium is not firmly bound, leaks out of the neuron and goes through a process of recycling across the cell membrane, while bethanidine is more firmly bound inside the neuron than bretylium, only slowly leaks out of the neuron and is not recycled back across the cell membrane.