The cardiovascular effects of benzquinamide were evaluated in anesthetized dogs. Intravenous benzquinamide, 0.5 to 5 μg/kg, caused tachycardia, elevated blood norepinephrine levels, frequent ventricular arrhythmias, and brief hypotension. Ganglionic blockade by hexamethonium prior to administration of benzquinamide prevented the tachycardia and alterations in norepinephrine levels but prolonged the period of hypotension. In isolated mesenteric arterial preparations benzquinamide interfered with contractile force generated by potassium chloride, norepinephrine, and prostaglandin F2α. It is concluded that benzquinamide directly relaxes vascular smooth muscle thereby producing in vivo reduced peripheral vascular resistance and hypotension, which are compensated for by reflex sympathetic activation.