Inflammation following an infection induces a range of nonspecific symptoms of sickness in animals and humans. The cytokine interleukin-1 (IL- 1) mediates many of the brain-mediated symptoms of sickness. Binding sites for IL-1 have been found in mouse brain, but not in the brains of rats. This raises questions as to the involvement of these neuronally localized IL-1 binding sites in the induction of sickness symptoms. Based on observations of IL-1 receptor mRNA in close vicinity to the vasculature in the mouse and rat brain, we studied the possibility that endothelial cells in the rat brain exhibit IL-1 receptors to transduce information to the brain. Ligand binding studies reveal that cultured endothelial cells of adult rat brain exhibit specific binding sites for rat IL-1β. Polymerase chain reaction experiments demonstrated that mRNA of the type I but not that of the type II IL-1 receptor is present in rat brain endothelial cells. Incubation of these endothelial cells with recombinant rat IL-1β showed a dose-dependent increase in interleukin-6, prostaglandin E2, and prostacyclin secretion. Intravenous administration of rat IL-1β to adult rats enhanced prostaglandin E2 immunoreactivity in endothelial cells of the brain microvasculature. These results indicate that functional type I IL-1 receptors are present on endothelial cells of adult rat brain. We postulate that circulating IL-1 can be translated by brain endothelial cells into other signals such as interleukin-6 or prostaglandins that have access to the brain and induce sickness symptoms.