The role of (+/-)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)-kainate and N-methyl-D-aspartate (NMDA) receptors in the rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM) on the central respiratory drive (CRD)-related activity of splanchnic sympathetic nerve activity (SNA) was examined in rats. SNA increased during inspiration (I peak) and postinspiration (PI peak). Bilateral microinjections of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; AMPA-kainate antagonist) or DL-2-amino-5-phosphonovaleric acid (APV; NMDA antagonist) into RVLM abolished the PI, but not the I, peak. Blockade of all excitatory amino acid receptors in RVLM with kynurenate, or mixtures of APV and CNQX, also failed to eliminate the I peak. Somatosympathetic responses were abolished by CNQX injection into RVLM, but were unaffected by APV. CNQX, but not APV, injection into CVLM increased the PI peak of SNA. Our findings suggest the following. 1) Both NMDA and AMPA-kainate receptors in RVLM are involved in the coupling between the sympathetic nervous system and CRD, which generates the PI peak seen in SNA. 2) The I peak of SNA is independent of excitatory amino acid transmission within RVLM. 3) There are different relative amounts of NMDA and AMPA-kainate receptors at synapses where respiratory and somatic inputs converge onto RVLM neurons. 4) Glutamatergic inputs to CVLM neurons modulate the coupling between SNA and CRD in RVLM.