Alpha adrenergic receptors can be differentiated into two distinct subtypes designated alpha 1 and alpha 2. Alpha 1 receptors represent the more classical alpha receptor population; they are located postjunctionally on effector cells and are blocked more potently by prazosin than yohimbine. Alpha 2 receptors are newly discovered; they are localized prejunctionally on neuron terminals and also postjunctionally on some effector cell types, and are blocked more potently by yohimbine than prazosin. Phentolamine and phenoxybenzamine block both alpha 1 and alpha 2 receptors. Alpha 2 receptors of noradrenergic neurons subserve an important autoinhibitory effect on norepinephrine release mechanisms. Norepinephrine discharged from the nerve terminal can feed back and activate prejunctional alpha 2 receptors, resulting in a diminution of subsequent neuroeffector transmission. On the other hand, nonselective alpha 1-alpha 2 blocking drugs inhibit alpha-mediated events in effector organs, but they also facilitate catecholamine release by freeing noradrenergic nerves from the alpha 2 feedback inhibition. Resulting increments in catecholamine concentrations may lead to a seemingly paradoxical sympathomimetic response owing to beta receptor activation in heart, vasculature, and perhaps other tissues. These pharmacodynamic complexities should be considered when nonselective alpha 1-alpha 2 blocking drugs are used in attempts to define cause-effect relationships in experimentally shocked animals.