We studied the effect of vagal afferents on the left ventricular contractile response [LVdP/dt(max)] to administration of sympathomimetic amines into the left circumflex coronary artery in conscious dogs. The positive inotropic effects of bolus administration of epinephrine, norepinephrine, and isoproterenol were greater during bilateral vagal cold block (BVB) than in the control state with the vagi intact (P<0.001). The inotropic potentiation observed with BVB was not due to vagal efferent interruptions, since parasympathetic efferent block with atropine did not potentiate the inotropic effects of intracoronary epinephrine (P>0.05). BVB also potentiated the inotropic effects of constant intracoronary infusion of epinephrine (P<0.01). BVB alone had no significant effect on LVdP/dt(max); however, BVB during constant intracoronary infusion of epinephrine did result in an increase in LVdP/dt(max) (P<0.05). We propose that the potentiation of the inotropic effects during BVB could result from either interruption of a vagal afferent-mediated negative feedback reflex and/or an unmasking of a sympathetic afferent-mediated positive feedback effect induced by BVB. However, the observations that ganglionic blockade also potentiated the contractile effects of epinephrine supports the concept that a negative feedback reflex does attenuate the inotropic effect of catecholamines in the control state. In conclusion, these data suggest that vagal afferents attenuate the positive inotropic effects of intracoronary administration of catecholamines via a cardiocardiac negative feedback reflex which occurs through a vagal afferent inhibition of sympathetic efferent activity back to the left ventricle.