During ACTH or cortisol infusion in ten recumbent normal men taking dexamethasone, the metabolic clearance rate of aldosterone increased by 50% as plasma cortisol was raised from low (2 μg/dl) to high concentration (50 μg/dl). Since splanchnic blood flow did not change, a greater efficiency of removal of aldosterone must have occurred, by means of displacement of aldosterone from high-affinity sites on plasma protein. At 37 C, equilibrium dialysis of low-cortisol plasma showed one-third of plasma aldosterone bound to albumin, and 24 to 28% bound to higher-affinity sites on other protein. As plasma cortisol increased, a progressively smaller fraction was tightly bound, approaching zero as transcortin was saturated with cortisol. The addition of large amounts of aldosterone to low-cortisol plasma displaced 14C-cortisol from transcortin binding sites. The results support earlier evidence that a significant fraction of plasma aldosterone is bound to transcortin, from which it is readily displaced by cortisol, resulting in an increased metabolic clearance rate of aldosterone by making a larger fraction available for removal from plasma.