Evidence has been obtained that clorgyline, a selective type A monoamine oxidase inhibitor (MAOI) with antidepressant properties, leads to decrease in the number of Beta-adrenergic receptors in rat brain, while pargyline, a selective type B MAOI, an ineffective antidepressant in our human studies, does not. A sequential study of these effects suggests that the clorgyline-induced Beta-adrenergic receptor changes are secondary to alterations in presynaptic mechanisms. These findings based on radioligand binding studies have now been supported by physiological studies of locomotor activity in response to the specific Alpha2-adrenergic agonist clonidine, and of in vitro catecholamine release in microsacs prepared from saline-treated and clorgyline-treated animals. The presynaptic changes are observed by three weeks of clorgyline treatment, whereas the post-synaptic physiological changes in norepinephrine stimulated cAMP occur some two weeks later. The MAOI side effects involving sleep and the cardiovascular system also appear to be adaptive in nature and selective for the type A MAOI. Pithed rats show enhanced blood pressure changes to sympathetic stimulation following clorgyline, but not deprenyl treatment.