To examine how the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) affects baroreflex regulation, reflex heart rate and renal nerve responses were recorded in anesthetized rats after bilateral injections of muscimol or bicuculline into the nucleus tractus solitarius (NTS). Blood pressure, heart rate, and renal nerve activity were increased by the GABA agonist muscimol and decreased by the GABA antagonist bicuculline. Control injections of the vehicle alone were ineffective. More importantly, all reflex responses later induced by infusing phenylephrine or sodium nitroprusside intravenously were reduced by muscimol. The magnitude of the reflex bradycardia and sympathoinhibition caused by phenylephrine, as well as that of the reflex tachycardia and sympathoexcitation caused by sodium nitroprusside, diminished after NTS injections of muscimol. By contrast, the same reflex responses tended to be enhanced after NTS injections of bicuculline, but most changes were not significant. If GABA acts on receptors located on second-order neurons in the NTS, then muscimol would inhibit those neurons, whereas bicuculline would prevent endogenous GABA from reaching them. Thus muscimol would reduce reflex responsiveness by inhibiting all second-order neurons, whereas bicuculline would enhance it by protecting the same neurons from inhibition by endogenous GABA.