Interleukin-6 (IL-6) is an important mediator in the interaction of the hypothalamo-pituitary-adrenal axis with the immune system. Recently, a direct influence of IL-6 on adrenal steroidogenesis has been demonstrated. Therefore, we designed a study to determine whether IL-6 is expressed within the normal human adrenal gland. The combination of in situ hybridization and specific immunostaining was eminently suited to identify the cell types producing IL-6. IL-6 messenger ribonucleic acid occurred in the inner zone of the adrenal cortex in anti-17 alpha-hydroxylase-positive steroid cells. Also, CD68-positive macrophages in the zona reticularis showed a positive signal. No reaction was seen in chromaffin cells. We conclude that under normal conditions, IL-6 is expressed in specialized adrenocortical cells. Therefore, IL-6 may play an important role as a paracrine or autocrine factor in a local immune-adrenal interaction.