Serotonin enhances (amplifies) the vasoconstrictor effect of norepinephrine not only on isolated large blood vessels and isolated perfused vascular beds but also in vivo. This amplification can be observed with endogenous serotonin released from aggregating platelets and with endogenous norepinephrine released from the adrenergic nerves in the blood vessel wall. It is due to an interaction between S2-serotonergic and alpha 1-adrenergic mechanisms. Combined S2-serotonergic and alpha 1-adrenergic antagonism is more effective than either one alone against contractions evoked with the combination of serotonin and an alpha 1-adrenergic agonist. In spontaneously hypertensive rats, S2-serotonergic antagonism alone does not reduce blood pressure but combined S2-serotonergic and alpha 1-adrenergic blockade lowers blood pressure more than alpha 1-adrenergic blockade alone. This suggests that the interaction between S2-serotonergic and alpha 1-adrenergic vasoconstrictor responses may play a role in the maintenance of high blood pressure.