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The present study was undertaken to determine whether gamma-aminobutyric acid in the paraventricular nucleus contributes to the regulation of cardiovascular function. Blood pressure and heart rate were recorded and plasma catecholamines were measured in conscious rats receiving microinfusions of either artificial cerebrospinal fluid or a gamma-aminobutyric acid antagonist, bicuculline methiodide, bilaterally into the paraventricular nucleus. Artificial cerebrospinal fluid had no effect on any of the recorded variables. In contrast, infusion of bicuculline into the region of the paraventricular nucleus produced increases in blood pressure (20 +/- 2 mm Hg), heart rate (110 +/- 11 beats/min), and plasma concentrations of norepinephrine (640 +/- 107 pg/ml) and epinephrine (1,266 +/- 267 pg/ml). Pretreatment with a ganglionic blocking agent abolished both the blood pressure (-1 +/- 2 mm Hg) and heart rate (5 +/- 18 beats/min) effects. Bilateral adrenal medullectomy reduced the changes in plasma norepinephrine concentrations (81 +/- 14 pg/ml) significantly and abolished the changes in plasma epinephrine concentrations (5 +/- 4 pg/ml). Conversely, adrenal medullectomy reduced the pressor effects (18 +/- 2 mm Hg) only slightly while the heart rate responses were attenuated (42 +/- 9 beats/min) by approximately 50%. These results suggest that an endogenous gamma-aminobutyric acid system exerts a tonic inhibitory effect on the sympathetic nervous system at the level of the paraventricular nucleus of the hypothalamus.