We have studied the expression of genes involved in glucocorticoid synthesis in the mouse developing lungs of male and female fetuses at gestation days (GDs) 15 to 18 (surge of surfactant GD17; term GD19). High levels of Steroidogenic Acute Regulatory protein, cytochrome P450 cholesterol side-chain cleavage, 3-hydroxysteroid dehydrogenase type 1, 21-hydroxylase, and 11-hydroxylase mRNAs were observed in 3 of 6 litters studied at GD15, and in none of 14 litters analyzed between GD 16 and 18. Of these three litters, two showed high expression levels for these 5 genes in lung tissues from female fetuses only, while in the remaining litter, only tissues from male fetuses presented high expression of these genes. In contrast, 11-hydroxysteroid dehydrogenase type 1 mRNA level was very low on GD 15 and presented a gradual increase between GD 15 and 18 with no sex difference. Our data indicate that, like the mature adrenal, the fetal lung expresses all the genes required in glucocorticoid synthesis from cholesterol. In addition, our results demonstrate that transient expression of these genes on GD15 in the fetal lung occurs for both male and female fetuses, two days before the surge of surfactant synthesis, which is stimulated by GCs.