We investigated the hypothesis that stimulation of metabotropic excitatory amino acid receptors in the ventrolateral medulla evokes cardiovascular responses. Thus, (15,3/?)-l-aminocyclopentane-l,3-dicarboxylic acid [(1S,3/J)-ACPD], a selective agonist of metabotropic excitatory amino acid receptors, was microinjected into the rostral or caudal ventrolateral medulla of halothane-anesthetized Sprague-Dawley rats. Microinjections of (lS,3/f)-ACPD (100 pmol-1 nmol) into the rostral ventrolateral medulla produced dose-dependent increases in mean arterial pressure (+20±4 mm Hg by 100 praol and +35±2 mm Hg by 1 nmol, p< 0.01 versus artificial cerebrospinal fluid) and integrated splanchnic sympathetic nerve activity (+17±3% and +46±4%, respectively, p<0.01), whereas (15,3/f)-ACPD microinjected into the caudal ventrolateral medulla decreased mean arterial pressure (-28±2 mm Hg by 100 pmol and -48±6 mm Hg by 1 nmol, p<0.01 versus artificial cerebrospinal fluid) and splanchnic sympathetic nerve activity (-24±4% and -49±5%, p<0.01). The blockade of ionotropic excitatory amino acid receptors by the combined injection of 2-amino-7-phosphonoheptanoic acid (200 pmol) and 6,7-dinitroquinoxaline-2,3-dione ( t is well appreciated that L-glutamate (Glu) is a primary excitatory neurotransmitter in the central nervous system. Glu or other excitatory amino acids (EAA) may act at receptors that are ligand-gated ion channels and are referred to as ionotropic EAA receptors.1 These receptors exhibit selective responsiveness to 7V-methyl-D-aspartic acid (NMDA), kainic acid, or a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA);