In this study, we determined whether either N-methyl-D-aspartate (NMDA) receptors or non-NMDA receptors in the nucleus tractus solitarii (NTS) participate in the baroreceptor reflex in rats. Microinjection of an NMDA receptor antagonist, MK-801, and a non-NMDA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, into the NTS decreased the sensitivity of the baroreceptor reflex by 51 and 41%, respectively. Simultaneous administration of both agents further reduced the sensitivity of the baroreceptor reflex to 28% of control. A competitive NMDA receptor antagonist, 2-amino-5-phosphono-valeric acid, also attenuated reflex bradycardia or tachycardia elicited by a single dose of phenylephrine or nitroprusside, respectively. Specificity of each antagonist's effects was supported by selective blockade of depressor responses produced by agonists that act at the NMDA and non-NMDA receptors, respectively. Results of this study indicate that both non-NMDA- and NMDA-sensitive receptors are involved in baroreceptor reflex transmission in the NTS.