A new role for the adrenal medulla as a regulator of adrenocortical function has been postulated. However, there has been no idea as to how such a cellular interaction within the human adrenal gland could take place. In this study we were able to demonstrate with the help of specific immunostaining of cortical and chromaffin cells, respectively, that the two endocrine systems are interwoven with each other to an astonishing degree. Protrusions, clusters, islets, and single cortical cells were made visible by immunostaining with an antibody against 17 alpha-hydroxylase cytochrome P450 enzyme. They occurred diffusely within the entire adrenal medulla, providing ample contact zones for paracrine interactions. Specific immunostaining for the neuroendocrine protein chromogranin-A identified the occurrence of chromaffin cells within all three zones of the human adrenal cortex, including the zona glomerulosa. In an ultrastructural analysis, cortical and chromaffin cells were found in all zones in direct apposition, providing the possibility for direct intercellular exchange. The close morphological colocalization of cortical and chromaffin cells revealed in this study may constitute the basis for the growing evidence of relevant intraadrenal paracrine mechanisms within the human adrenal gland.