The effects of L-N-G-nitro arginine methyl ester (L-NAME), L-N-G-monomethyl arginine (L-NMMA), L-arginine and D-N-G-nitro arginine methyl ester (D-NAME) on morphine antinociception were studied in rite mouse using two nociceptive assays, the abdominal constriction and tail flick rests. In the abdominal constriction test, L-arginine and D-NAME (20 mg/kg) and no effect on the number of abdominal constrictions, nor did they affect the responses due to morphine (1 mg/kg). L-NAME and L-NMMA (10 mg/kg) exhibited marked antinociception when administered on their own and morphine antinociception was enhanced in mice pretreated with these two agents. In the tail flick test, similar doses of L-NAME, L-NMMA, L-arginine and D-NAME had no effect on their own. D-NAME had no effect on morphine analgesia, L-NAME and L-NMMA enhanced morphine antinociception, and L-arginine attenuated morphine antinociception. Therefore, increasing the levels of NO attenuates morphine antinociception, while lowering the levels enhances it. These results suggest that NO may play an, important role in pain perception, and probably in the antinociceptive responses to morphine.