In this study, we aimed to reveal the interaction between the tricyclic antidepressant amitriptyline and a1-adrenoceptor antagonist prazosin in mice by using an analgesiometric device hot-plate. Amitriptyline (10 mg/kg) has analgesic effect as expected. Neither of the prazosin doses (0.1, 0.2, 0.5, 1 mg/kg) displayed analgesic effect alone. The combination of lower doses of prazosin (0.1, 0.2, 0.5 mg/kg) with amitriptyline (10 mg/kg) potentiated the antinociceptive effect of this drug. However, the relatively higher dose of prazosin (1 mg/kg) did not effect amitriptyline analgesia. Thus we conclude that the antinociceptive effect of amitriptyline is potentiated by low doses of prazosin.