We have demonstrated that ethanol-induced motor incoordination is modulated by cerebellar adenosine A 1 receptor. This study represents an extension into another important brain motor area, the striatum that, unlike cerebellum, has high density of both A 1 and A 2A receptors. Direct intra-striatal micro-infusion of Ro15-4513 (0.05, 0.5, 1 ng), a partial inverse-agonist of benzodiazepine, significantly and nearly dose-dependently attenuated ethanol-induced motor incoordination indicating mediation of ethanol’s motor incoordination by striatum. Intra-striatal A 1-selective agonist N 6-cyclohexyladenosine (CHA; 1, 2, 4 ng), A 1 = A 2A non-selective agonist, 5′-N-ethylcarboxamidoadenosine (NECA; 1.5, 3, 6 ng), and A 1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 25, 50, 100 ng) dose-dependently accentuated and attenuated, respectively, ethanol-induced motor incoordination, strongly suggesting modulation by striatal adenosine A 1 receptor. Intra-striatal DPCPX significantly antagonized not only ethanol-induced motor incoordination but also its potentiation by intra-striatal CHA, R-(+)-N 6-(2-phenylisopropyladenosine) (R-PIA), or NECA. No change in motor coordination occurred after the highest dose of CHA, R-PIA, or NECA followed by saline. Similarly, the highest intra-striatal dose of Ro15-4513 or DPCPX neither altered motor coordination or locomotor activity indicating relative selectivity of interaction with ethanol. Nearly 25-fold higher dose of A 2A-selective agonist, CGS-21680, compared to CHA was necessary to produce a comparable potentiation of ethanol’s motor incoordination perhaps suggesting a lack of or less significant striatal A 2A involvement. Intra-striatal pertussis toxin (0.5 μg) pre-treatment markedly attenuated ethanol-induced motor incoordination as well as its potentiation by intra-striatal CHA. These results support that striatum is one of the brain motor areas mediating the motor impairing effects of acute ethanol and that the latter’s modulation occurs via A 1-selective receptors coupled to pertussis toxin-sensitive G proteins.