Our previous studies demonstrated that intravenous (IV) administration of the selective dopamine (DA) D2 receptor agonist quinpirole (LY171555) induces a pressor response in conscious Sprague-Dawley (S-D) rats through a central mechanism. The present study was designed to identify the neurons which medicate this pressor response. Injection of quinpirole (1-150 μg/kg) into the 4th ventricle produced a greater pressor response of a more rapid onset than similar injections into the lateral ventricle in conscious, freely moving S-D rats, suggesting a site of action in brainstem. Further, microinjections (5-10 μg/kg in 200 nl) of quinpirole into major hypothalamic nuclei of conscious, freely moving rats elicited no pressor response. Uni- or bilateral microinjections of quinpirole (5 μg/200 nl) into the posterior region of nucleus tractus solitarius (P-NTS) caused a consistent increase in mean arterial pressure (MAP) (Max = 12.4 ± 1.1 mmHg, n = 12) with a rapid onset (< 30 sec) in unanesthetized decerebrate S-D rats, while microinjections into the anterior region of NTS, area postrema, C1/A1 regions, raphe obscurus nucleus, locus coeruleus or regions 0.5 mm lateral, superior or inferior to P-NTS produced little or no response. The pressor response induced by bilateral microinjections of quinpirole into P-NTS was not different from that of unilateral microinjection. The pressor response to microinjections of quinpirole into P-NTS was abolished by pretreatment with metoclopramide (5 mg/kg, IV or 25 μg/200 nl, P-NTS injection; 5 min before), a selective DA D2 antagonist that crosses the blood-brain barrier. These data demonstrate that DA D2 receptors on neurons located in P-NTS mediate the central pressor action of quinpirole. © 1990.