Studies of the mode of action of antidepressant treatments and the biological basis of depression have recently concentrated on monoamine neurotransmitter receptors. This paper reviews the studies relating to alpha 2-adrenoceptors. Chronic administration of some but not all antidepressant treatments to animals alters the number and function of brain alpha 2-adrenoceptors. In man, platelet alpha 2-adrenoceptors have been widely studied as a quantifiable peripheral model of central alpha 2-adrenoceptors. The majority of studies have not identified clear differences in platelet alpha 2-adrenoceptors between drug-free depressed patients and control subjects, nor have they identified unequivocal effects of antidepressant treatments. Methodological problems and choice of radioligand may contribute to discrepancies between studies. Central alpha 2-adrenoceptor function in man has been assessed by measuring neuroendocrine and physiological responses to clonidine. Despite considerable variation in procedure, in diagnostic criteria, and in the interval since previous treatment, most studies find the growth hormone response attenuated in depressed patients. This provides the strongest evidence to date of an abnormality of alpha 2-adrenoceptors in depression. However, it seems likely that none of the measures to date adequately mirrors the function of the cortical and limbic receptors implicated in the pathophysiology of depression. It is also likely that no single neurotransmitter abnormality is common to all depressed subjects and that future studies should be aimed at the inter-relationship and dysregulation of several neurotransmitter systems.