The action of 5-hydroxytryptamine (5-HT) to potentiate vasoconstrictor responses to noradrenaline has been studied using the rat isolated perfused mesenteric artery. Receptor antagonists have been employed to compare the vascular receptors which mediate the vasoconstrictor and potentiating actions of 5-HT. In preparations pretreated with methysergide (1 mumol X 1(-1)), cyproheptadine (1 mumol X 1(-1)) or fluoxetine (1 mumol X 1(-1)) the vasoconstrictor response to 5-HT (1 mumol X 1(-1)) was abolished, while ketanserin (1 nmol X 1(-1)) antagonized the response by 90%. In contrast, only methysergide antagonized the sensitizing effect of 5-HT, while the other three antagonists exerted no effect on this action. In view of the different sensitivities of the vasoconstrictor and potentiating effects of 5-HT to antagonist drugs, it is suggested that the vascular receptors which mediate these actions are different.