Interleukin-1 (IL-1) is an inflammatory peptide hormone, with potent neuroendocrine effects. IL-1 stimulates the central nervous system production of corticotropin-releasing hormone (CRH), growth hormone (GH), thyroid-stimulating hormone (TSH), and somatostatin, and inhibits the secretion of prolactin and luteinizing hormone (LH). Interleukin-1 receptor antagonist (IL-1ra) is a novel cytokine, recently purified, characterized, and cloned. IL-1ra is a pure endogenous antagonist of IL-1:IL-1 function is modulated not only by local levels of IL-1, but also by the levels of IL-1ra. We have localized by in situ hybridization histochemistry IL-1ra mRNA in rat brain, in areas of importance to neuroendocrine function, such as the paraventricular nucleus (PVN) of the hypothalamus, hippocampus, as well as cerebellum. These findings indicate that IL-1ra is produced in brain in areas of relevance to the regulation of neuroendocrine function and suggest that IL-1ra may modulate the neuroendocrine effects of IL-1.