CRF and IL-1 receptors were identified, characterized, and localized in brain, endocrine, and immune tissues. CRF receptors with comparable kinetic and pharmacological characteristics were localized in the anterior and intermediate lobes of the pituitary, in brain areas involved in mediating stress responses, and in the macrophage-enriched marginal zones of the spleen. The discrete localization of IL-1 receptors in neurons of the hippocampus provides further support for the role of IL-1 as a neurotransmitter/neuromodulator/growth factor in the CNS. The neuroendocrine effects of IL-1 may be mediated through actions of the cytokine in brain. However, given the high densities of IL-1 receptors in the anterior pituitary and testis, direct effects of the cytokine at the pituitary or gonadal levels seem highly likely. Overall, these data support a role for IL-1 and CRF in coordinating and integrating the brain-endocrine-immune responses to physiological, pharmacological, and pathological stimuli.