Adrenergic neuron blockade was induced by guanethidine in the pithed rat preparation. The pressor response to spinal electric stimulation was inhibited. The guanethidine blockade was reversed or prevented not only by tricyclic antidepressants but also by tripelennamine (an H1 antihistamine), tranylcypromine (a monoamine oxidase inhibitor) and viloxazine (a new antidepressant structurally unrelated to tricyclic antidepressants). Since these compounds all share neuronal uptake inhibitory activity, it seems that this property per se is sufficient to reverse/prevent the adrenergic neuron blockade induced by guanethdine.