Ephedrine and phenylpropanolamine (PPA) (10 mg/kg) pretreatment intraperitoneally (IP) potentiated the antinociceptive effects of subcutaneous (SC) morphine (5 mg/kg) and codeine (60 mg/kg) in mice using the tail-flick method. Prior administration of propranolol (6 mg/kg, SC) 10 min before the sympathomimetics had no effect on this action. Phentolamine (2 mg/kg, SC), on the other hand, abolished the enhancing effects of ephedrine and PPA on opioid antinociception. Prazosin (2 mg/kg, SC) pretreatment did not significantly affect the potentiation of opioid antinociception by ephedrine and PPA, while yohimbine (4 mg/kg, SC) effectively antagonised this enhancing effect. None of the adrenoceptor antagonists had any effect on the tail-flick reaction time on their own in the doses used, and neither did they affect opioid antinociceptive responses. It is concluded that ephedrine and PPA potentiate the antinociceptive effects of morphine and codeine, most probably through an action on ₂-adrenoceptors.