The increase in arterial pressure and heart rate elicited during exercise are produced by descending central command and by feedback from contracting limb muscles. Previous studies from this laboratory have demonstrated that neurons in the ventrolateral medulla (VLM) that project to the intermediolateral (IML) columns of the thoracic spinal cord are involved in the mediation of the pressor response to contraction of hind limb muscles. This study determines if these VLM neurons utilize excitatory amino acids (EAA) as the neurotransmitter at the synapse on IML neurons. The arterial pressure and heart rate responses to static muscular contraction, elicited by stimulation of the L7 and S1 ventral roots, and to electrical stimulation in the caudal hypothalamus were examined in anesthetized cats. Both muscular contraction and hypothalamic stimulation elicited significant increases in arterial pressure and heart rate. Intrathecal administration of the broad spectrum, postsynaptic EAA antagonist, kynurenic acid, greatly reduced (−77%) the pressor response to muscular contraction. A smaller (−27%) decrease in the magnitude of pressor response elicited by muscular contraction was produced by intrathecal administration of 2-amino-4-phosphonobutyric acid which acts on a presynaptic EAA receptor. Neither antagonist affected the heart rate responses associated with muscular contraction or the cardiovascular responses to hypothalamic stimulation. These results indicate that the pressor response elicited by feedback from contracting hind limb muscles is mediated through an excitatory amino acid synapse in the spinal cord.