Synaptosomes (P2) were prepared from cerebral cortices of control rats and from those which had received clorgyline (1 mg/kg/day for 21-28 days) or desipramine (10 mg/kg/day for 21-28 days). Following incubation with [3H]noradrenaline (500 nM/15 min, 37 degrees C), aliquots of the synaptosomes were gently filtered onto Whatman GF/A filters and superfused with Krebs buffer (pH 7.5, 37 degrees C) for a maximum period of 2 h. During this time, the basal efflux of tritiated materials (approximately 75% noradrenaline) together with K+-evoked release of the amine and metabolites, were measured. Chronic antidepressant drug regimens increased the K+-stimulated release, but its attenuation by clonidine was not altered. Thus, chronic antidepressant drug regimens do not apparently alter presynaptic alpha 2-adrenoceptors. These results suggest that the reported antidepressant drug induced decreases in [3H]clonidine binding, occur on sites which are postsynaptic to noradrenergic neurones. Following the chronic antidepressant drug regimens, the sensitivity of the [3H]noradrenaline release process to Ca2+ is significantly increased. This change may explain the enhanced K+-evoked release which follows the antidepressant drug regimens. It is proposed that this increased sensitivity of the [3H]noradrenaline release process may be an adaptation to the decrease in neuronal firing which have been reported following antidepressant drug treatments.