BACKGROUND The mediodorsal thalamic nucleus has extensive connections with prefrontal cortex, which is considered as seat of cognition. It also receives connections from sleep-wakefulness regulating areas in the brainstem and hypothalamus. Decreased volume and degeneration of mediodorsal thalamic nuclei have been reported in schizophrenia and fatal familial insomnia, respectively. In both conditions, the sleep is abnormal. OBJECTIVE To study the role of mediodorsal thalamic nuclei in sleep wakefulness in rats. METHODS Neurotoxic lesion of mediodorsal thalamic nuclei with ibotenic acid was performed in adult male Wistar rats and sleep wakefulness was recorded. The recordings were taken on 2nd, 7th and 14th days after lesion and compared with the baseline recordings. In order to study the diurnal changes, lesion recordings were of 24h duration. We also performed L-glutamate excitation of mediodorsal thalamic nuclei in another set of animals. After L-glutamate microinjection, sleep wakefulness was recorded for 4h. The recordings were obtained in a digital acquisition system (BSL 4.0 MP 36, Biopac Systems, Inc., USA). RESULTS In the present investigation, ibotenic acid lesion of mediodorsal thalamic nuclei reduced the wakefulness and increased paradoxical sleep, which contradicts the reports from earlier lesion studies in cats. Glutamate excitation of mediodorsal thalamic nuclei produced prolonged wakefulness. CONCLUSIONS The results suggest that the mediodorsal thalamic nuclei augments arousal in the ascending reticular wake promoting pathways in contrast to the earlier reports that mediodorsal thalamic nucleus is involved in generation of slow wave sleep. The present study adds another evidence for the role of thalamus in sleep-wake regulation.