Clonidine is an antihypertensive agent with a primary action mediated by alpha adrenergic stimulation in the central nervous system, thus inhibiting sympathetic efferent activity. Serotonin activates a cardiogenic hypertensive chemoreflex which induces discharges of sympathetic efferent neurons. The purpose of this study was to determine the effects of intravenous clonidine upon the thoracic sympathetic efferent discharges in chloralose-anesthetized dogs, their peripheral autonomic receptors being blocked with atropine, propranolol, and phentolamine. Efferent nerve traffic was quantified using a Schmitt trigger and Digital PDP8/e computer. Control spontaneous activity (tone) following autonomic blockade was normalized at 100%. Serotonin (100 μg/ml, 2 ml, left atrium) caused an increase in the reflex efferent sympathetic activity to 192% ± 16% of control (p < 0.001). Following clonidine, the tone was decreased to 63% ± 6% of control, and the reflex sympathetic discharge elicited by serotonin was significantly (p < 0.001) reduced from 192% to 116% ± 9% of control tone (before clonidine). The attenuation of the reflexly elicited discharge was significantly (p < 0.05) greater than the attenuation of the tone. In four dogs that did not receive atropine, the vago-vagal reflex sinus bradycardia induced by serotonin was not affected by clonidine. © 1981 American Heart Association, Inc.