γ-Aminobutyric acid (GABA) and the GABA antagonist bicuculline methiodide were used to investigate the role of GABAergic transmission in the rostral and caudal ventrolateral medulla in 12- to 13-wk-old spontaneously hypertensive (SH) (n = 7) and normotensive, control Wistary-Kyoto (WKY) (n = 7) rats. Animals were anesthetized with urethan (1.25 g/kg sc), paralyzed with gallamine triethiodide (10 mg/kg iv), and artificially ventilated. Femoral arterial and venous catheters were inserted for the measurement of mean arterial pressure (MAP) and heart rate responses and for intravenous infusions. The ventral surface of the brain stem then was exposed. The responsiveness of the rostral ventrolateral medulla to GABA was compared in SH and WKY rats using unilateral microinjections (30 nl) of GABA at 1, 10, and 100 mM concentrations, which produced significantly (P < 0.05) larger decreases of MAP in SH rats compared with WKY at the 10 and 100 mM concentrations (-37.3 ± 2.8 mmHg for SH vs. -27.3 ± 2.7 mmHg for WKY at 100 mM). Tonic GABAergic inhibition was gauged using bilateral microinjections (30 nl) of bicuculline (2 and 4 mM) into the rostral ventrolateral medulla, which caused significantly larger increases in MAP in the WKY group (+84.8 ± 8.5 mmHg at 4 mM) compared with the SH group (+14.9 ± 5.8 mmHg at 4 mM). In contrast, the ability to drive sympathetic outflow by microinjection of L-glutamate in the rostral ventrolateral medulla was not significantly different between WKY and SH rats. Inhibition of the caudal ventrolateral medulla with bilateral tetrodotoxin injections (30 nl, 10 μM) increased MAP in the WKY group (+40.3 ± 3.3 mmHg), but did not significantly change MAP in the SH group (-4.9 ± 7.6 mmHg). The tetrodotoxin in the caudal ventrolateral medulla also attenuated the MAP response to bicuculline (4 mM) injected bilaterally into the rostral ventrolateral medulla in the WKY group (+12.6 ± 4.5 mmHg at 4 mM), but did not significantly alter the response in the SH group. These results indicate that withdrawal, but not impairment, of GABAergic input into the rostral ventrolateral medulla, originating from or traveling through the caudal ventrolateral medulla, may contribute to the elevation of arterial pressure in the SH rat.