The cytokines are a group of pluripotential proteins that affect the functioning of the immune system as well as the hypothalamic-pituitary axis. This review summarizes recent findings related to the effects of interleukin (IL)-1, IL-2, IL-6, and tumor necrosis factor-α (TNF-α) on the neuroendocrine system Cytokine binding sites on anterior pituitary cells (IL-6, IL-1, IL-2) and in the hypothalamus (IL-6, IL-1) suggest a role for these factors in the regulation of hormone secretion. IL-6, IL-1, IL-2, and TNF-α each regulate the synthesis and release of anterior pituitary hormones in vitro. In addition, the cytokines enhance hypothalamic-releasing factor production by the medial basal hypolhalamus and, at least for IL-6, the median eminence as well. The neuroendocrine mechanisms activated by central and peripheral administration of IL-1 are probably unrelated. Multiple points of interaction with the neuroendocrine system and redundancy of effects suggest that a variety of inflammatory insults distinguished by different cytokine patterns may still result in a prototypical activation of the hypothalamic-pituitary-adrenal axis.