The primary mechanism leading to hypersecretion of aldosterone during sodium depletion in the dog is increased activity of the renin-angiotensin system. Loss of salt and water leads to renin release and increased aldosterone and corticosterone secretion. Plasma renin was elevated within one hour after diuretic administration. The increase in corticosterone production was transient; return of corticosterone to the control level appears to be mediated by the negative corticosteroid feedback mechanism via the anterior pituitary. It is suggested that the role of ACTH in aldosterone production during sodium depletion is a supportive one. In severe sodium depletion decreased plasma sodium and increased plasma potassium concentrations further augment the hypersecretion of aldosterone.