Aldosterone enters red blood cells (RBC) to a greater extent at 37 C than at lower temperatures. The ratio of 3H-aldosterone concentration in RBC to that in plasma increases from 0.2 at 4 C to 0.7 at 37 C when cortisol concentration is low. Increasing plasma cortisol increases the RBC/plasma aldosterone ratio. When plasma transcortin (CBG) is saturated with cortisol, the RBC/plasma ratio of 3H-aldosterone approaches 0.93, the ratio observed in RBC incubated in 4% albumin solution. The effects of plasma cortisol and temperature on the RBC/plasma ratio reflect an affinity of aldosterone for plasma CBG greater than the affinity for plasma albumin or RBC. Hepatic extraction averages 92% of plasma and RBC aldosterone. Neither hepatic extraction nor renal extraction (less than or equal to 20%) is significantly altered by changing plasma cortisol concentration. Whole blood MCR of aldosterone is unaffected by redistribution of aldosterone from plasma to RBC when plasma cortisol increases, but both plasma cortisol and the temperature at which blood is separated affect the RBC/plasma ratio of 3H-aldosterone and thus change the calculated plasma MCR. The RBC transport of aldosterone, and its dependence on temperature and plasma cortisol, must be taken into account in the evaluation of plasma aldosterone concentration.