Abstract: Interleukin-6 (il-6) and tumor necrosis factor α (TNFα) and their mRNAs are present in the human, rat, and bovine adrenal cortex. The release of these cytokines from adrenal cells is regulated by factors that alter adrenal function (e.g., ACTH, angiotensin II, interleukin-1). IL-6 and TNF type 1 receptors are also present on adrenocortical cells. Exposure to IL-6 increases cortisol or corticosterone release from human, bovine, and rat adrenal cells. IL-6 increases basal and ACTH-stimulated aldosterone release, but inhibits angiotensin II-stimulated aldosterone secretion from bovine adrenal cells. IL-6 increases dehydroepiandrosterone (DHEA) release from human cells, but decreases DHEA secretion from bovine cells. TNFα inhibits corticosterone release from normal rat adrenal cells or fragments, but increases corticosterone release from cholestatic rat adrenal slices. TNFα decreases cortisol release from bovine and fetal human adrenal cells, but increases cortisol release from adult human adrenal cells. TNFα inhibits aldosterone secretion from rat and bovine adrenocortical cells. TNFα does not affect DHEA secretion from fetal human adrenocortical cells, but inhibits basal and ACTH-stimulated DHEA release from bovine adrenal cell. Because IL-6 and TNFα are produced in the adrenal gland and modify adrenal steroid secretion, these cytokines may function as intraadrenal factors in the regulation of adrenal steroid secretion.