The compound ambrein was isolated from ambergris, which is commonly used as an analgesic in the Saudi folklore medicine. The LD50 of ambrein, given intraperitoneally (i.p.) in mice, was found to be high (7.5 g/kg), and ambrein proved to be a safe compound in this species. In the hotplate test, ambrein was found to possess antinociceptive activity in mice at doses which did not sedate or incapacitate the animals. By the i.p. administration route, ambrein produced antinociception in mice at a dose as low as 10 mg/kg. The antinociceptive activity of ambrein (250 mg/kg i.p.) was inhibited by a noradrenergic neurotoxin (DSP-4) and by naloxone, methysergide or prazosin. It was not influenced by a serotonin depletor, p-chlorophenylalanine. The possible mechanism of ambrein antinociception is discussed.