The mammalian adrenal cortex is a heterogeneous collection of cells which are arranged in specific regions or concentric zones. Each zone is thought to carry out a specific function (produce a particular steroid hormone) and respond to a specific regulator. There appears to be considerable overlap, however, in that the same stimulatory factor may influence and some steroids can be produced and secreted by more than one zone. The developmental nature of adrenocortical zonation is not well understood. Whether the cells in each zone arise as distinct and unique entities or are derived in some fashion from a common precursor is not at all clear. The guinea pig, a cortisol producer like the human being, is utilized as an animal model because of the relatively large size of the adrenal, a corticomedullary ratio of approximately 80:1, and the relative ease by which outer and inner zones can be separated. The outer zone is composed of the zona glomerulosa and zona fasciculata, while the inner zone consists of the zona reticularis. It is the latter zone which is of particular interest since little is known of its functional nature, steroidogenic capability, and specific regulation. A. Role of ACTH in regulating the zona reticularis. The role of ACTH in regulating the zona fasciculata is well characterized; however its role in regulating the zona reticularis is unclear. When dexametasone was administered to animals to suppress secretion of endogenous ACTH, the zona fasciculata reduced steroid production and atrophied, as expected, but the zona reticularis was unaffected. B. Role of ACTH in regulating specific activities in the zona reticularis. In contrast to the zona fasciculata, lipoprotein receptor activity and steroid synthesis are not stimulated by ACTH. On the other hand adenylate cyclase activity, ascorbic acid (vitamin C) depletion, and hydrolysis of cholesteryl ester stores are promoted by ACTH in the zona reticularis as they are in the zona fasciculata. Thus, the zona reticularis has retained certain specific responses to ACTH while losing others.