The effect of nicotine on morphine induced antinociception was studied using the tail-flick test. A low dose of nicotine (0.0001 mg/kg) which did not induce any antinociception, potentiated the morphine antinociceptive response dose-dependently. The opioid antagonist naloxone decreased the response of morphine and morphine plus nicotine. The muscarinic receptor antagonist atropine decreased the nicotine-induced potentiation of the morphine response. Sulpiride, pimozide, SCH 23390, phenoxybenzamine, propranolol, methysergide, metergoline, hexamethonium and mecamylamine did not alter the antinociception induced by nicotine and morphine. It is concluded that the potentiation of morphine-induced antinociception by nicotine may be mediated through a cholinergic mechanism.