Segments of the rat vena cava preincubated with [3H]noradrenaline and superfused with [3H]noradrenaline-free solution containing desipramine and corticosterone were stimulated electrically (standard parameters: 150 mA, 0.3 ms, 0.66 Hz; duration 6 min). In some experiments the stimulation parameters were modified in order to obtain similar absolute release values despite the presence of an alpha-adrenoceptor agonist or antagonist or of 5-hydroxytryptamine (5-HT). In a first set of experiments, the vascular segments were first exposed to an alpha-adrenoceptor ligand, which was kept present throughout the remainder of superfusion, and then to 5-HT. The release-inhibiting effect of 5-HT was attenuated by the alpha 2-adrenoceptor agonists clonidine and B-HT 920 whereas it was enhanced by the alpha-adrenoceptor antagonists phentolamine and idazoxan. The alpha 1-adrenoceptor antagonist prazosin did not change the 5-HT-induced inhibition of noradrenaline (NA) release. In a second set of experiments, 5-HT was administered first and kept present in the superfusion fluid for the remainder of the experiment. In the presence of 5-HT, the overflow-inhibiting effects of B-HT 920 and clonidine and the overflow-enhancing effect of idazoxan were reduced. The results demonstrate that activation of one kind of receptor decreased the inhibition of noradrenaline release produced by activation of the other. These effects were not the consequence of the change of release per se induced by the interacting drugs, since they also occurred when the release was adjusted to similar levels by modification of the stimulation parameters.(ABSTRACT TRUNCATED AT 250 WORDS)