Neurotransmitter receptors, located on the nerve terminal from which this transmitter is released, are termed presynaptic autoreceptors. Evidence for their existence and functional role has been obtained by experiments carried out in vitro and in vivo. For example, noradrenergic, dopaminergic, serotoninergic, cholinergic and GABAergic neurons are endowed with presynaptic autoreceptors mediating a negative feedback loop. These receptors play a physiological role in the fine regulation of transmitter release in the peripheral and/or central nervous system, and, thus, may modulate any function controlled by the respective neurones. The physiological role of inhibitory or facilitatory autoreceptors for peptide cotransmitters on, e.g., noradrenergic and serotoninergic neurones is less well established. Alterations of the number or responsiveness of autoreceptors may play a role in the pathogenesis of diseases which are related to a disturbed function of the respective neurones in the peripheral or central nervous system. As an example, the potential importance of autoinhibitory alpha 2-adrenoceptors and autofacilitatory beta 2-adrenoceptors (activated by the cotransmitter adrenaline; both receptors located on sympathetic nerve fibres) and of autoinhibitory presynaptic 5-HT1B receptors (located on central serotoninergic nerves) in the development of essential hypertension is discussed. Autoreceptors may play a role in the therapeutic effect of currently available drugs, and it is probable that new classes of drugs which act predominantly via this site will be developed.