Epinephrine has been implicated in the genesis of some forms of hypertension. We have investigated the effects of epinephrine on vasoconstrictor responses evoked by adrenergic stimuli in the isolated perfused rat kidney. Low concentrations of epinephrine (2.5 - 5 X 10(-9) M) increased the amplitude of vasoconstrictor responses evoked by electrical stimulation of the renal adrenergic nerves. These concentrations of epinephrine had no effect on the basal perfusion pressure of the kidney or on the amplitude of vasoconstrictor responses evoked by exogenous norepinephrine. The potentiating effect of epinephrine persisted after infusion of the amine had ceased. Kidneys that had been perfused with 3H-epinephrine accumulated radioactivity, which could then be released by renal nerve stimulation. Cocaine (3 X 10(-5) M) reduced the renal accumulation of 3H-epinephrine and abolished both the persistent potentiating effect of the amine and the release of radioactivity evoked by subsequent nerve stimulation. The potentiating effect of epinephrine infusion was abolished by the beta 2-selective adrenergic receptor antagonist ICI 118,551 (3 X 10(-8) M), but not by the beta 1-selective adrenergic receptor antagonist atenolol (10(-6) M). These results indicate that concentrations of epinephrine that can be achieved during acute stress can enhance the amplitude of neurogenic vasoconstrictor responses. This effect appears to be mediated via a prejunctional beta 2-adrenergic receptor. The persistent nature of this effect may be due to the neuronal accumulation and subsequent release of epinephrine.