The modulatory effects of vasodilatory peptides on noradrenaline release from sympathetic nerve terminals have been studied in the rat portal vein model. Transmural field stimulation of the longitudinally mounted vein preparation evoked concomitant increases in the [3H]noradrenaline overflow and the integrated tension. Both responses were abolished by guanethidine or tetrodotoxin, whereas only the tension response was blocked by phentolamine. CGRP and VIP, both being present in intramural nerve fibers in the rat portal vein, were compared with atriopeptin II for modulatory effects. CGRP (100 nM) had no effect on the overflow of [3H]noradrenaline or the integrated tension response to transmural stimulation. VIP (30 nM) and atriopeptin II (30 nM) both caused significant reductions of both [3H]noradrenaline overflow and the integrated tension. These results indicate that the decreased tension response to transmural stimulation in the presence of VIP or AP II reflects the sum of both pre- and postsynaptic inhibitions.