The presynaptic mechanisms appear to be involved in the regulation of noradrenaline release during nerve stimulation. The first one. mediated by beta-adrenoceptors, operates at low frequencies of nerve stimulation, leading to an increase in transmitter release. The second one, mediated through alpha-adrenoceptors, is triggered when higher concentrations of the transmitter are reached in the synaptic cleft, leading to inhibition of transmitter release, probably through a restriction in the availability of calcium for the secretory process. 2. It is postulated that part of the anti-hypertensive effects of drugs like clonidine, alpha-methyldopa and beta-receptor-blocking agents may be related to their long-term effects on presynaptic adrenoceptors.