To investigate if adenosine A2A receptor stimulation in vivo modulates dopamine D3 receptor binding, we analyzed the effects of 2-[p-(carboxyethyl)-phenylethylamino]-5'-N-ethylcarboxyamidoade nosine (CGS 21680) on the binding properties of the selective D3 receptor agonist [N-propyl-2,3,-3H]4aR,10bR-(+)-trans-3,4,4a,10b-tetrahydro-4 -n-propyl2H,5H-[1]benzopyrano[4,3-b]1,4-oxazin-9-ol ([3H]PD 128907) in the rat forebrain using quantitative autoradiography. Intraperitoneally administered CGS 21680 (0.1-3 mg/kg) increased the Kd and Bmax values of [3H]PD 128907 binding in the islands of Calleja and in subregions of the caudate-putamen. These results suggest that stimulation of adenosine A2A receptors in vivo causes alterations in the binding characteristics of dopamine D3 receptors in the basal ganglia, and that this effect may relate to the neuroleptic-like effect of adenosine A2A receptor agonists.