The effect of GABAA receptor agonist muscimol and antagonist picrotoxin on the hypotensive action of clonidine was investigated. Moreover, the GABA concentration in some brain areas in spontaneously hypertensive (SHR) and normotensive (WKY) rats was studied. It was demonstrated that co-dosage clonidine with the agonist or the antagonist modulates hypotensive effect of drug. Our data suggest that the clonidine interaction with these agents occurs at the level of GABAergic neurotransmission since clonidine and both compounds have been proved to influence the function of GABAergic neurons. It was also shown the lower GABA content in some brain areas of SHR than WKY rats. Based on the findings could be implicate that the stronger action of clonidine on blood pressure in SHR is also connected with alterations of other neurotransmitter systems involving in its hypotensive effect.