We determined the effects of bilateral microinjection of muscimol and excitatory amino acid receptor antagonists into the medullary lateral tegmental field (LTF) on the changes in sympathetic nerve discharge (SND), mean arterial pressure (MAP), and phrenic nerve activity (PNA, artificially ventilated cats) or intratracheal pressure (spontaneously breathing cats) elicited by right atrial administration of phenylbiguanide (PBG; i.e., the Bezold-Jarisch reflex) in dial-urethane anesthetized cats. The PBG-induced depressor response (-66 ± 8 mmHg; mean ± SE) was converted to a pressor response after muscimol microinjection in 2 of 3 spontaneously breathing cats and was markedly reduced in the other cat; however, the duration of apnea (20 ± 3 vs 17 ± 7 s) was essentially unchanged. In 7 paralyzed, artificially ventilated cats, muscimol microinjection significantly (P < 0.05) attenuated the PBG-induced fall in MAP (-39 ± 7 vs -4 ± 4 mmHg) and the magnitude (-98 ± 1 vs -35 ± 13%) and duration (15 ± 2 vs 3 ± 2 s) of the sympathoinhibitory response. In contrast, the PBG-induced inhibition of PNA was unaffected (3 cats). Similar results were obtained by microinjection of an N-methyl-D-aspartate (NMDA) receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid, into the LTF. In contrast, neither the cardiovascular nor respiratory responses to PBG were altered by blockade of non-NMDA receptors with 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo-[f]quinoxaline-7-sulfonamide. We conclude that the LTF subserves a critical role in mediating the sympathetic and cardiovascular components of the Bezold-Jarisch reflex. Moreover, these data show separation of the pathways mediating the respiratory and cardiovascular responses of this reflex at a level central to bulbospinal outflows to phrenic motoneurons and preganglionic sympathetic neurons.