The conversion of cortisol (F) to cortisone (E) is catalyzed by 11beta-hydroxysteroid dehydrogenase type 2. The present study was designed to investigate the changes of F and E plasma concentration as an indirect measurement of 11beta-hydroxysteroid dehydrogenase activity in infancy and childhood. Plasma samples were obtained from 262 healthy children and adolescents aged 1 d to 18 y. Plasma F and E were measured, using specific radioimmunoassays after extraction and automated Sephadex LH 20 chromatography. The F/E ratio was calculated to assess 11beta-hydroxysteroid dehydrogenase activity. During the first year of life, plasma F levels rose significantly (r(2) = 0,24; p = 0.01), and thereafter no further increase was seen until adulthood (r(2) = 0.01; p = 0.86). In contrast, plasma E significantly decreased during the first year of life (r(2) = -0.35; p<0.001) and stayed unchanged thereafter (r(2) = 0.02; p = 0.81). As a consequence, the F/E ratio rose significantly during the first year (r(2) = 0.67; p<0.001) but did not change afterward (r(2) = 0.001; p = 0.99). During the first year of life, there is a change from the predominance of E, with low mineralocorticoid receptor affinity, to F, with high mineralocorticoid receptor affinity. This shift corresponds to the declining plasma concentrations of aldosterone during infancy. The changes may indicate a not yet recognized, significant change of 11beta-hydroxysteroid dehydrogenase isoenzyme activity or alterations in the secretion of F and E, which may be of relevance for the development of arterial blood pressure in infancy.