We sought to establish whether neurons of the C1 area of the rostral ventrolateral medulla (RVL) mediate changes in arterial pressure and heart rate evoked by topical application of drugs to the ventral medullary surface of the rat. Animals were anesthetized, paralyzed, and ventilated. The ventral surface was mapped with L-glutamate, and a restricted zone was identified from which L-glutamate, as well as kainic acid, bicuculline, strychnine, carbachol, or physostigmine, increased arterial pressure and heart rate. The hypertensive effects of carbachol and physostigmine were blocked by previous local application of atropine but not hexamethonium. Application of gamma-aminobutyric acid (GABA) or glycine to this area produced hypotension and bradycardia. Located caudal to the trapezoid bodies and lateral to the pyramids, this area corresponded to points with lowest threshold for pressor responses evoked by electrical stimulation and overlapped the distribution of epinephrine-synthesizing cells of the RVL. Processes arising from these neurons were identified reaching and contacting the ventral surface. Unilateral lesions involving the C1 area or phenylethanolamine-N-methyltransferase-labeled descending axons derived from this area imparied by greater than 70% the response to ipsilateral application of L-glutamate, GABA, or glycine to the ventral surface. We suggest that neurons within the C1 area of RVL adjacent to or including epinephrine cells may mediate cardiovascular changes elicited from a restricted chemosensitive zone of the ventral medullary surface of the rat.