The sleep-wakefulness continuity is sensitive to a wide range of agents with pharmacological activity. There is some strong evidence about the role of nitric oxide (NO) as an intercellular messenger in the central physiological mechanisms. The effects of 7-nitro indazole (7-NI 15, 30, 60 mg kg-1; intraperitoneal, i.p.), a selective inhibitor of neuronal nitric oxide synthase (NOS) and L-arginine (500, 1000 mg kg-1, i.p.), a NO precursor, on pentobarbital (35 mg kg-1, i.p.) sleep were examined in mice. Loss of the righting reflex was used to determine the start of sleep. Sleep latency and sleeping time were evaluated in each experiment. 7-Nitro indazole (7-NI 30 mg kg-1; i.p.), had no apparent effect on sleep latency but significantly increased sleeping time (P < 0.02) on pentobarbital sleep in mice. L-Arginine had no effect on both parameters. These findings suggest that NO might be an important modulator of sleep regulation and implicate that inhibition of release and/or synthesis of NO might lead to changes in the maintenance of sleep.