Young and old Long-Evans rats respond with fevers of equal magnitude and duration to the brain administration of interleukin-1β (IL-1β). Here, we characterized brain regional mRNA expression of cytokine and neuropeptide components in response to the brain administration of IL-1β. We used specific and highly sensitive RNase protection assays to determine mRNA changes for IL-1β, IL-1 receptor type I (IL-1RI), IL-1R accessory proteins I and II (IL-1R AcP I and II), IL-1 receptor antagonist (IL-1Ra), transforming growth factor-β1 (TGF-β1), glycoprotein 130 (gp 130), leptin receptor (OB-R), neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) in the cerebellum, parieto-frontal cortex, hippocampus, hypothalamus, and midbrain of male young (3-5 months) and old (24-26 months) Long-Evans rats. In both young and old rats, IL-1β induced a significant up-regulation of cerebellar IL-1Ra, IL-1RI, and TGF-β1 mRNAs; hippocampal TGF-β1 mRNA; hypothalamic IL-1β, IL-1Ra, TGF-β1, and gp 130 mRNAs; and midbrain IL-1β and TGF-β1 mRNAs. There were no age-related differences in any cytokine mRNA levels under basal or IL-1β-stimulated conditions. Levels of hypothalamic POMC mRNA were different between age groups under basal and stimulated conditions. IL-1R AcP I and leptin receptor did not change in any brain region from either young or old rats, suggesting specificity of transcriptional changes. The data show that old Long-Evans rats are not defective in their capacity to develop an appropriate cytokine response to the brain administration of IL-1β. The implications of these findings for neuroimmunological-neuroinflammatory and neurotoxic/neurodegenerative processes are discussed.