We demonstrated an adenosine A,, receptor-mediated disinhibition of medium spiny projection neurons using intracellular recording and the whole-cell patch-clamp recording applied to these cells, visually identified in thin rat striatal slices. The A,, receptor agonist 2-b-(2-carboxyethyl) phenylethylaminol-5’-N-ethylcarboxamido adenosine (CGS-21680; 0.3-l 0 PM) suppressed GABAergic synaptic transmission onto these cells in a manner inhibited by the A,, receptor-selective antagonist (E)-8-(3, 4-dimethoxystytyl)-l, 3-dipropyl-7-methylxanthine(0.1-l. O PM). The A, receptor antagonists had no effect on the CGS-21680-induced suppression. Analysis of spontaneous miniature inhibitory synaptic currents indicated that suppression of intrastriatal GABAergic synaptic transmission was attributable to presynaptic, but not postsynaptic, A,, receptors. Therefore, the A,, receptor may regulate striatal output activity by relieving GABA-mediated inhibition of the medium spiny projection neurons, which explains the ability of purinergic agents to affect motor control.