Much evidence suggests that tumor necrosis factor-alpha (TNF-alpha) is involved in the regulation of physiological sleep. However, it remains unclear whether peripheral administration of TNF-alpha induces sleep in rats. Furthermore, the role of the vagus nerve in the somnogenic actions of TNF-alpha had not heretofore been studied. Four doses of TNF-alpha were administered intraperitoneally just before the onset of the dark period. The three higher doses of TNF-alpha (50, 100, and 200 microg/kg) dose dependently increased nonrapid eye movement sleep (NREMS), accompanied by increases in electroencephalogram (EEG) slow-wave activity. TNF-alpha increased EEG delta-power and decreased EEG alpha- and beta-power during the initial 3 h after injection. In vagotomized rats, the NREMS responses to 50 or 100 microg/kg of TNF-alpha were attenuated, while significant TNF-alpha-induced increases in NREMS were observed in a sham-operated group. Moreover, the vagotomized rats failed to exhibit the increase in EEG delta-power induced by TNF-alpha intraperitoneally. These results suggest that peripheral TNF-alpha can induce NREMS and vagal afferents play an important role in the effects of peripheral TNF-alpha and EEG synchronization on sleep. Intraperitoneal TNF-alpha failed to affect brain temperature at the doses tested, thereby demonstrating that TNF-alpha-induced sleep effects are, in part, independent from its effects on brain temperature. Results are consistent with the hypothesis that a cytokine network is involved in sleep regulation.