The role of calcium (Ca ions) as the stimulus-secretion coupling agent has been firmly established. The proposed research project involves a continuation of the study of the action of Ca ions on the isolated cat adrenal gland, perfused in situ (Douglas & Rubin, 1961) and also on cat cortical cell suspensions prepared by trypsin digestion. With these preparations, the effects on hormone release can be measured on intact cells without interference from other systems, e.g., ant. pituitary. Previous work from this laboratory has shown that a translocation of Ca ions accompanies both catecholamine and steroid release. In light of the apparent importance of cyclic AMP in hormone action, studies will be carried out to elucidate the interaction of Ca ions and cyclic AMP in hormone production and release from the adrenal gland. The adrenal cortex may provide a rather unique secretory system with which to study the action of Ca ions, since the corticosteroid does not appear to be stored in pre-wrapped packets (granules), but after stimulation with ACTH, the newly-synthesized hormone is immediately secreted. In the adrenal medulla, catecholamine is sequestered within membrane-bound granules and, after the initiation of the appropriate stimulus, is immediately released by exocytosis. Thus, in order to help define the molecular events associated with the secretory process, the relation between cyclic AMP and calcium in these two seemingly disparate secretory systems should be elucidated. Further insight into the cardinal role of calcium and cyclic AMP in the regulation of hormonal secretion would, of course, lead to a more basic understanding of hormonal secretory mechanisms in general.