The presence and cellular localization of interleukin-1 beta immunoreactivity (irIL-1) in and around the brain was investigated using immunocytochemistry on Bouin's fixed vibratome brain sections of control and endotoxin-treated rats. Peripheral administration of endotoxin resulted in the appearance of irIL-1 in cells in the meninges, choroid plexus, brain blood vessels and in non-neuronal cells in the brain parenchyma. Using monoclonal and polyclonal antibodies to macrophage and astrocyte antigens, the endotoxin-induced irIL-1 positive cells could be identified as macrophages in the meninges and choroid plexus (ED2), perivascular cells (ED2) and ramified microglial cells (GSA-I-B4 isolectin). Our data demonstrate a pathway for the induction of non-specific sickness symptoms in response to endotoxin.