Interleukin-10 (IL-10), originally designated a cytokine synthesis inhibitory factor, inhibits the synthesis of the pro-inflammatory cytokines IL-1 and tumor necrosis factor by stimulated human and mouse monocytes/macrophages; these cytokines are involved in the regulation of sleep. To determine if IL-10 reduces spontaneous sleep, we injected murine recombinant IL-10 intracerebroventricularly into rats prior to light onset. Non-rapid eye movements sleep was reduced. The behavioral responses to IL-10 were abolished by heat-inactivation of this cytokine. We believe these to be the first observations of central nervous system actions for this cytokine. These results further support the hypothesis that cytokines are involved in the regulation of sleep, and suggest an additional mechanism whereby sleep may be altered in response to an activated immune system.