Previous studies have reported that information from carotid chemoreceptors activates sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM) exclusively via N-methyl-D-aspartic acid (NMDA) receptors. In this study, we examined the possible involvement of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors in the RVLM on sympathetic chemoreceptor reflex in pentobarbitone anaesthetised, vagotomised and artificially ventilated rats. Carotid chemoreceptor stimulation with brief N2 inhalation increased splanchnic sympathetic nerve activity and arterial pressure in animals that had received an intravenous injection of the non-competitive NMDA receptor blocker, MK-801 (2 mg/kg). RVLM sympathetic premotor neurons could also be activated by brief hypoxia in the presence of MK-801. However, microinjection of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, a selective AMPA/kainate receptor antagonist, 2 mM, 100 nl) into the RVLM after intravenous MK-801 abolished the hypoxia evoked sympathoexcitatory response. These results demonstrate that AMPA/kainate receptors in the RVLM are involved in the chemoreceptor reflex pathway.