Epinephrine-containing neurons of the rostral ventrolateral medulla (RVL) (the C1 group of Hökfelt) in the rat are primarily unilaterally innervated by neurons in the nucleus tractus solitarius (NTS) and in turn project to autonomic spinal neurons. In this study, we investigated whether the C1 area of the RVL mediates the vasodepressor responses (VDR) induced by either electrical stimulation of the vagus nerve or carotid sinus stretch. In all experiments, C1 neurons were localized immunocytochemically with antibodies to phenylethanolamine N-methyltransferase (PNMT). Bilateral lesions of the C1 area decreased arterial pressure (AP) and heart rate (HR) to spinal cord transection levels and blocked the VDR induced by vagal stimulation and carotid sinus stretch. Combined lesions of the contralateral NTS and C1 area ipsilateral to the stimulated vagus nerve maintained AP and HR at normal levels, and totally blocked the VDR to vagal stimulation and carotid sinus stretch. Since projections from the vagus nerve to NTS are bilateral and those from NTS to C1 unilateral, the combined contralateral NTS/ipsilateral C1 lesions isolated and interrupted the ipsilateral NTS-C1 pathway and, therefore, blocked the baroreceptor reflex. The results are consistent with the hypothesis that neurons in the NTS synapsing in or projecting through the C1 area mediate the baro- and cardiopulmonary mechanoreceptor reflex.