In rats bearing a unilateral 6-hydroxydopamine lesion of the dopaminergic nigro-striatal pathway, stimulation of adenosine A(2) receptors by CGS 21680 reduced the contralateral turning behavior induced by L-3,4-dihydroxyphenylalanine (L-DOPA). Administration of CGS 21680 completely blocked the contralateral turning induced by the dopamine D-1 receptor agonist, SKF 38393, and reduced the turning induced by the dopamine D-2 receptor agonist, LY 171555. Quinolinic acid lesion of the striatum or 6-hydroxydopamine lesion of the dopaminergic nigro-striatal neurons demonstrated that [H-3]CGS 21680 binding sites are associated to striatal intrinsic neurons. This study provides evidence for a negative postsynaptic interaction of both dopamine D-1 and D-2 receptors with adenosine A(2) receptors.