Abstract: The present study investigated the possible role of nitric oxide (NO) in the development of morphine- and deltorphin II-induced electroencephalographic (EEG) seizures in rabbits. Central administration of morphine and deltorphin II (100 ?g/icv/toto) produces EEG seizure activity in rabbits, associated with wet-dog shakes, myoclonic twitches and convulsive activity.. L-NG-nitro arginine methyl ester (L-NAME) (300 ?g/i.c.v./toto) did not induce significant EEG or behavioral changes whereas when injected 15 min before i.c.v. morphine or deltorphin II (100 ?g/icv/toto) dose dependently prevented the EEG ictal episodes, the spiking activity and the synchronized EEG pattern induced by morphine or deltorphin II. The inhibitory effect of L-NAME on morphine or deltorphin II seizures was dose-dependently reversed by L-arginine (300 ?g/icv/toto) but not by D-arginine. Finally, glyceryl trinitrate on its own (300 ?g/icv/toto) significantly increased morphine or deltorphin II seizures in the rabbit and it was also able to reverse the inhibition on morphine or deltorphin II seizures operated by L-NAME. These results provide evidence that NO may play a significant role in the development of opioids-EEG seizures