IL-1 beta has been implicated in central nervous system effects, including activation of the hypothalamic-pituitary-adrenal axis. Less is known concerning the role of IL-6 in brain. To compare and contrast IL-1 beta and IL-6 effects on brain, rats were administered intraperitoneal injections of IL-1 beta, IL-6 or control vehicle (3-8 mu g/rat), perfused 150-180 min post-injection, and brains and pituitaries were processed for Fos immunolabeling. IL-1 beta induced Fos expression in corticotrophin-releasing factor (CRF) neurons of paraventricular nucleus (PVN) of the hypothalamus, and anterior pituitary gland. IL-6 also induced immunolabeled Fos in the anterior pituitary gland, however, it did not induce Fos expression in CRF neurons of PVN. Data suggest that IL-6 may directly activate the anterior pituitary gland, whereas IL-1 beta may exert its effect on the pituitary directly and/or indirectly via activation of CRF neurons in the PVN.