GABAergic agents microinjected into the nucleus tractus solitarius (NTS) influence blood pressure (BP) and plasma vasopressin (VP) levels. The direct-acting GABAergic agonist muscimol (3.75-160 pmol) microinjected bilaterally into the NTS of chloralose-anesthetized, paralyzed, ventilated rats increased BP without significantly altering heart rate. Similar results were obtained using the indirect GABA agonist nipecotic acid (10 nmol), a GABA uptake blocker. In contrast, blocking the action of GABA with bicuculline (5 pmol) elicited a small but consistent decrease in BP. Injections of the vehicle (artificial cerebrospinal fluid) into the NTS or GABAergic agents in an area lateral to the NTS did not alter BP. Unilateral injection of muscimol into the NTS did not elicit immediate pressor responses as did bilateral injections; unilateral muscimol injections following destruction of the contralateral NTS produced a pressor response similar to that seen following bilateral muscimol administration. Stimulation of GABA receptors within the NTS by either muscimol or nipecotic acid resulted in an increase in plasma VP levels. The elevated levels of plasma VP contributed to the pressor response elicited by stimulation of GABAergic receptors as evidenced by the decrease in BP observed following the intravenous administration of a VP pressor antagonist during the pressor response. These studies indicate that tonically active GABAergic mechanisms within the NTS influence BP and VP release, and provide further evidence that VP can be involved in cardiovascular responses elicited from the NTS.