Metabolic clearance rates (MCR) of aldosterone, cortisol, DOC, corticosterone, and progesterone were simultaneously measured by constant infusion in 8 control subjects before and during an ACTH infusion (12.5 U/4 h). Plasma levels of aldosterone and cortisol, the heat-labile plasma protein-bound fraction of aldosterone, and hepatic blood flow as estimated by the fractional clearance ofindocyanine green, were concomitantly determined. The mean MCR of aldosterone, cortisol, and DOC increased to a peak value of 26%, 23%, and 22%, respectively, above baseline values. The increase was already significant (P < 0.001) 30 min after the beginning of the ACTH infusion. In contrast, no consistent changes occurred in the MCR of corticosterone and progesterone or in hepatic blood flow. ACTH induced a marked fall in the heat-labile plasma protein-bound fraction of aldosterone. Plasma levels of aldosterone and cortisol increased by 190 and 250%, respectively. A significant negative correlation (r = −0.423, P < 0.01) between the MCR and the heat-labile proteinbound fraction of aldosterone was observed. We suggest that competitive interactions in the protein binding properties of various steroids account for the selective effect of ACTH on the MCR of aldosterone, cortisol, and DOC.