Adrenalectomized weanling rats injected with [3H]aldosterone plus excess RU486, with or without a range of doses of nonradioactive aldosterone or corticosterone, show tissue-specific patterns of competition for tracer binding to mineralocorticoid receptors (MR). From detailed dose-response curves, corticosterone in vivo shows approximately 3% the apparent affinity of aldosterone for MR in colon and kidney, approximately 30% for those in the heart, and approximately 300% in the hippocampus. We interpret these data as evidence that 1) relatively low levels of aldosterone cross the blood-brain barrier; and 2) specificity-conferring mechanisms in addition to the exclusion of corticosterone from epithelial MR are required for selective aldosterone action in sodium homeostasis.