Excitatory amino acid (EAA) receptors in the rostral part of the ventrolateral medulla (VLM) have been shown to mediate pressor responses elicited by stimulation of various peripheral afferent fibers as well as other central nuclei. This study tested the hypothesis that these receptors are a critical component in the central pathway mediating the powerful pressor response that is produced by stimulation of a group of neurons within a circumscribed region in the rostral dorsomedial medulla (RDM). In anesthetized rabbits, the pressor response elicited by unilateral microinjection of glutamate into this RDM region was measured before and after injection of kynurenic acid (Kyn), a broad-spectrum EAA receptor antagonist, into the physiologically identified pressor region of either the ipsilateral or contralateral rostral VLM. The pressor response to RDM stimulation was greatly reduced (to 24 +/- 4% of control) 5-10 min after injection of Kyn (but not the vehicle solution) into the ipsilateral rostral VLM; this response returned completely to its control value within 30-60 min after Kyn injection. By contrast, after Kyn injection into the contralateral rostral VLM, the pressor response to RDM stimulation was not affected (106 +/- 15% of control). The results indicate that the descending pressor pathway from the RDM to the spinal cord is mediated by EAA receptors in the rostral VLM pressor region. Furthermore, the pathway from the RDM to the rostral VLM is predominantly, if not exclusively, ipsilateral.