The objectives of the research described in this application are to investigate the fate of the adrenal medulla chromaffin granule after it has released its secretory products by exocytosis. Biochemical and pharmacological procedures will be used in the perfused isolated cow adrenal gland to study the ability of the empty chromaffin granule to function in the a) synthesis, b) storage and c) release of newly synthesized catecholamines and chromogranin-proteins. Incorporation of radioactive precursors will be used to follow the synthesis of chromaffin granule components and to estimate the turnover of chromaffin granule components. Morphological studies in in vivo rabbit adrenal medullar and in perfused isolated cow adrenal glands will be carried out in an attempt to provide a morphologic interpretation of the biochemical findings obtained in this study. It is felt that a combination of biochemical and morphological approaches offers the best opportunity for gaining an understanding of the full life cycle of the chromaffin granule.