Cardiovascular effects of chemical stimulation of the rostral ventrolateral medulla were studied in pentobarbital-anesthetized, paralyzed rats to examine the medullary GABAergic mechanisms responsible for cardiovascular regulation. Bilateral microinjections of 3-mercaptopropionic acid (10 micrograms), an inhibitor of gamma-aminobutyric acid (GABA) synthesis, into the ventrolateral medulla produced an increase in blood pressure and heart rate. Unilateral microinjection of nipecotic acid (3 micrograms), a reuptake inhibitor of GABA, elicited a fall in arterial pressure and heart rate. Bilateral microinjections of bicuculline (100 pmol), a GABA antagonist, into the ventrolateral medulla produced a sustained increase in arterial pressure and heart rate and, in addition, inhibited the hypotensive action induced by veratrine (0.3 mg/kg, i.v.). Lesioning of the rat nucleus tractus solitarii did not alter GABA content in the rostral ventrolateral medulla. These results support the hypothesis that in the rostral ventrolateral medulla, there exist GABAergic mechanisms involved in cardiovascular regulation. It seems unlikely that the GABAergic mechanisms originate mainly from neurons in the nucleus tractus solitarii.