The effect of quipazine on vasoconstrictor responses to periarterial sympathetic nerve stimulation (NS: 8 Hz, 2 ms, 30 s) and to exogenous norepinephrine (NE) were investigated in the isolated perfused mesenteric arteries of the spontaneously hypertensive rats (SHR) and the normotensive Wistar Kyoto rats (WKY). Quipazine (100 nM) potentiated the pressor response to NS significantly more than that to NE in both SHR and WKY. This agent (30 and 100 nM) also significantly increased the NS-evoked 3H overflow in the [3H]NE pretreated mesenteric vasculature of SHR, but not of WKY, suggesting facilitation of transmitter release. The summation of the pre- and postsynaptic effects of quipazine may account for its greater amplifying effects on NS in SHR, while this agent may act mainly postsynaptically in WKY. The presynaptic action is not attributable to alpha-adrenoceptor blockade but probably to a serotonin-like agonistic action, and the postsynaptic action appears to be mediated by ketanserin-sensitive (5HT2) receptors.