The involvement of α₂-adrenoceptors in the antinociception induced by the tricyclic antidepressants amitriptyline and imipramine was investigated in mice by using the hot-plate and abdominal constriction tests.The antinociception produced by amitriptyline(15mg/kg, i.p.) and imipramine(15mg/kg, i.p.) was prevented by reserpine(2mg/kg, i.p.) and yohimbine(3-10mg/kg, i.p.) but not by naloxone(1mg/kg, i.p.), atropine(5mg/kg, i.p.), CGP 35348(100mg/kg, i.p.) and prazosin(1mg/kg, i.p.).On the basis of the above data, it can be postulated that amitriptyline and imipramine exerted their antinociceptive effect by activation of α₂-adrenoceptors.Administration of the α_2A-adrenoceptor antagonist BRL 44408(1mg/kg, i.p.) prevented amitriptyline and imipramine antinociception, whereas the α_2B/C-adrenoceptor antagonist ARC 239(10mg/kg, i.p.) was ineffective.These data indicate that the enhancement of the pain threshold produced by amitriptyline and imipramine is mediated by activation of α_2A-adrenoceptors.Neither tricyclic antidepressants nor the antagonists used impaired mouse performance evaluated by the rota-rod and hole-board tests.