AbstractThe action of immune‐system‐derived cytokines to stimulate the release of corticotropin‐releasing factor (CRF) from the hypothalamus and the consequent elaboration of ACTH and release of corticosteroids has provided an especially useful model to investigate the nature of the intercommunication of neuroendocrine and immunological pathways. Substantial evidence exists to support the production of cytokines, such as interleukin‐1 (IL‐1) α and β, within the mammalian central nervous system. The mechanisms and neuronal circuitries involved in the effects of these cytokines of peripheral and central origin on the activity of neuroendocrine CRF motoneurons and the hypothalamic‐pituitary‐adrenal axis are described. Also included is a discussion of the influence of IL‐1 on transduction signals controlling the release and the biosynthesis of CRF in the parvocellular division of the paraventricular nucleus of the hypothalamus and the relationship between these two distinct intracellular processes. The relebance of using immediate early genes as indices of neuronal activity in immune‐challenged rats and the possible roles of c‐fosand NGFI‐B within neuroendocrine CRF motoneurons are outlined. Finally, the effects of acute immune response on neuroendocrine functions and brain neuronal activation are presented.