The effects of selective A(1) and A(2A) adenosine receptor compounds in two mouse models of acute nociception were studied: acetic acid-induced writhing and the hot plate assays. Stimulation of A(1) receptors by 2-chloro-N(6)-cyclopentyl-adenosine (CCPA, 0.01-0.1 mg/kg, i.p.; A(1)K(i)=6 nM) or blockade of A(2A) receptors by 5-amino-7-(beta-phenylethyl)-2-(8-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261, 1-10 mg/kg, i.p.; A(2)(A)K(i)=1.3 nM) produced anti-nociceptive effects. At the highest dose tested, CCPA and SCH58261 reduced the number of writhings by 79 and 99%, respectively. On the contrary, the A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (A(1)K(i)=2.8 nM) and the A(2A) agonist 2-(4-[2-carboxyethyl])phenethylamino-5'-N-ethylcarboxamido-adenosine-hydrochloride (GGS21680) produced pro-nociceptive effects in both tests. These findings suggest for the first time that blockade of A(2A) adenosine receptors produces anti-nociceptive effects.