At birth, the lung develops a Na⁺ absorbing phenotype that is vital for lung function and which depends upon epithelial Na⁺ channels that are formed from three subunits (α-, β- and γ-ENaC). The development of this phenotype requires prior exposure to circulating glucocorticoids but the physiological basis of this dependence is not clear (Olver et al., 2004). However, dexamethasone can activate the α-ENaC promoter with no apparent effect upon β- and γ-ENaC and, since α-ENaC is the only subunit vital for lung function, it has been suggested that glucocorticoid-evoked α-ENaC expression may be important to the development of the pulmonary Na⁺ absorption (Sayegh et al., 1999). However, the concentrations of cortisol, the natural glucocorticoid, needed to elicit this response are unknown which makes it difficult to assess the significance of glucocorticoid-evoked α-ENaC transcription to lung maturation in utero. In the present study we therefore explored the extent to which cortisol could activate a luciferase-linked reporter construct (KR-1-pGL3) containing a 2.2 kb upstream region of the human α-ENaC gene (Sayegh et al., 1999; Richard et al., 2004). Whilst our data (Fig 1) show clearly that cortisol activates this construct as effectively as dexamethasone, the EC₅₀ value was 108 ± 13 nM (estimated by least squares regression), which is ~20-fold greater that our recently published value for dexamethasone (~5 nM, see Richard et al., 2004). Assays (Gitau et al., 2001) of blood collected from the umbilical vein have shown that cortisol levels reach ~0.7 μM after normal vaginal delivery and ~0.3 μM after elective Caesarean section. The cortisol levels experienced during birth are therefore sufficient to cause maximal activation of the α-ENaC promoter (Fig 1).