In the hot-plate test in mice, the antinociceptive action of the alpha 2-adrenoceptor agonist, UK 14,304, was abolished by the alpha 2-adrenoceptor antagonist, idazoxan, the potent alpha 2A-adrenoceptor antagonist, RX 821002 and the preferential alpha 2A-adrenoceptor antagonist, BRL 44408. In contrast, the preferential alpha 2B- (and alpha 2C)-adrenoceptor ligands ('antagonists'), ARC-239, BRL 41992 and prazosin were inactive. The preferential alpha 2A-adrenoceptor partial agonist, guanfacine, partially inhibited UK 14,304-induced antinociception. Further, guanfacine BRL 44408 reversibly elicited submaximal antinociception. It is concluded that alpha 2A-adrenoceptors mediate antinociception in mice.