This is an attempt to investigate the effect of gamma-aminobutyric acid (GABA), a well-known major inhibitory neurotransmitter in the central nervous system, on the blood pressure response in rats and to elucidate the mechanism of its action. GABA injected into a femoral vein of the rat produced a dose-related fall in blood pressure followed by a secondary pressor response. The depressor response evoked by GABA was clearly blocked by pretreatment with chlorisondamine, diazepam and picrotoxin but was unaffected by atropine, prazosin and debrisoquin. GABA-induced pressor responses were significantly attenuated by pretreatment with prazosin or picrotoxin, while not affected by atropine, diazepam, debrisoquin and chlorisondamine. These experimental data suggest that GABA causes biphasically depressor and pressor responses in rats, and that the hypotensive activity evoked by GABA may be exerted through activation of GABAergic receptors and hypertensive activity due to stimulation of the adrenergic alpha-receptors, which appears to be associated with GABAergic receptors.