An antisense oligodeoxynucleotide which specifically blocked the production of the glutamate receptor subtype NMDAR1 was administered to the nucleus tractus solitarius (NTS) in order to examine the role of this receptor in baroreflex control of heart rate. Baseline blood pressure and heart rate were unchanged by NTS treatment with the antisense oligodeoxynucleotide to the NMDAR1 receptor subunit. However, the reflex bradycardia evoked in response to the hypertension induced by bolus administration of phenylephrine was significantly attenuated following bilateral NTS antisense oligodeoxynucleotide treatment. Administration of the corresponding mismatched antisense oligodeoxynucleotide did not significantly alter the reflex bradycardia. These data indicate that NMDAR1 receptors are involved in neurotransmission in the baroreflex arc at the level of the NTS. The specificity of antisense oligodeoxynucleotides may prove to be a useful technique to analyze the role of receptor subtypes mediating neurotransmission in central pathways.