Renins of different molecular weights such as big renin and small renin are known to exist in several species. However, little of anything is known about the mechanism of release of big renin from the kidney and other organs, the factors which regulate it, and the relationships between the mechanism of big renin secretion to that of small renin. The studies proposed here are designed to investigate the mechanism of big renin and small renin secretion and the factors which regulate it. To do this, model tissue systems, procedures and techniques developed in our laboratory will be used. These include slices and cell preparations from kidneys and submaxillary glands and a radioimmunoassay procedure developed in our laboratory for the direct measurement of renin. Since this procedure measures big renin and small renin directly, it is of special value in studies related to the mechanism of big renin and small renin release from renal and extrarenal sources. A better understanding of the mechanism of secretion of renins of different molecular weights is necessary in order to develop better means by which their secretion could be altered and actions controlled. It is proposed, therefore, to use procedures available in our laboratory to investigate the mechanism of release of big renin in conjunction with that of small renin in vitro. The results will be important in our understanding of the role of big and small renin in the etiology of hypertension.