Although melatonin has been implicated in several neurophysiological systems, data on the relationship of melatonin with psychosis such as schizophrenia are limited and contradictory. Chronic effects of melatonin on sensorimotor gating deficits have also not been investigated yet. We investigated the neurobehavioral effects of chronic administration of melatonin in pinealectomized (Px) and ovariectomized (Ovx) rats. Px or Ovx or both operations were carried out together to the rats. The control group of rats was sham operated. A sham ovariectomy was carried out to Px rats, and vice versa. Fifth month later, melatonin (5mg/kg) or vehicle was injected to rats for 28 days. Then, prepulse inhibition (PPI) of acoustic startle reflex, startle amplitude and startle reflex latency was measured. Locomotor activity, accelerod performance measurements, novel object recognition and passive avoidance tests were also evaluated. Px and Px+Ovx rats had impaired PPI compared to control rats. Melatonin reversed the impairments of PPI induced by Px or Px+Ovx. While melatonin treatment had no effect on locomotor activity of control rats, it significantly increased the locomotor activity of Px and Px+Ovx rats. Melatonin treatment (5mg/kg/day, 28 days) reversed the locomotor hyperactivity caused by Ovx. Accelerod performance, passive avoidance, and object recognition responses of Px, Ovx or Px+Ovx rats were not different from the control group. Our results indicate that chronic melatonin deficiency by reason of Px results in impairment of PPI reflex and replacement of melatonin exerts beneficial effects on the impaired PPI reflex in Px and Ovx rats. Thus, melatonin may be useful in the treatment of some disorders characterized by sensorimotor gating deficits such as schizophrenia.