Some evidence suggests that sleep deprivation might impair synaptic plasticity and produce oxidative stress in the hippocampus. However it is not clear whether impairment of long-term potentiation depends on the oxidative stress evoked by sleep deprivation protocol. In this study we aimed to investigate the effects of a 21-day sleep deprivation period on long-term plasticity taking into account the stressful effect of sleep deprivation. Sleep deprivation was carried out using the multiple platforms method on adult male Wistar rats. Long-term potentiation was studied in the medial perforant pathway-dentate gyrus synapses. Elevated T test was applied, and blood corticosterone levels were measured. Lipid peroxidation products in whole brain and hippocampus were determined. No significant difference was found between the sleep deprived, pedestal and cage control groups at the end of the 21-day period when corticosterone levels were compared. The results of the elevated T test indicated that sleep deprivation did not change the anxiety-like behavior of the animals. When compared with cage or pedestal control groups, sleep deprived rats displayed elevated malondialdehyde levels, and decreased superoxide dismutase and glutathione peroxidase activities together with impaired long-term potentiation maintenance. It can be argued that 21-day SD may impair the maintenance of long-term potentiation evoked in the dentate gyrus, and the balance between oxidant and antioxidant defenses of the hippocampus. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.