Sumatriptan and 5-benzyloxytryptamine are ligands with high affinity for 5-HT1D receptors in the caudate nucleus. Both compounds contracted canine saphenous veins, in vitro. Benzyloxytryptamine was less potent as a contractile agonist than sumatriptan which was less potent than serotonin. In high concentrations (greater than 10(-5) M) serotonin-induced contraction resulted, in part, from activation of alpha-adrenoceptors as determined by blockade of contraction with prazosin (10(-6) M) and idazoxan (10(-6) M). Likewise, benzyloxytryptamine but not sumatriptan also activated contractile alpha-receptors in the canine saphenous vein. Furthermore, benzyloxytryptamine antagonized contraction to sumatriptan in an apparently non-competitive fashion. Thus, benzyloxytryptamine, although possessing some alpha-receptor agonist activity, like sumatriptan, can interact with serotonin receptors in canine saphenous veins. Although effects of sumatriptan and benzyloxytryptamine quantitatively differed in canine saphenous veins, both agents showed similar affinity and agonist efficacy at 5-HT1D receptors in brain. These studies may reflect potential differences between the 5-HT1D receptor in brain and the 5-HT1-like receptor in canine saphenous veins.