Northern blotting and hybridization histochemistry were used to evaluate the ontogeny and cellular distribution of the mRNAs of the cytochrome P-450 enzymes: cholesterol side-chain cleavage (P-450scc), 17 alpha-hydroxylase (P-450(17 alpha] and 21-hydroxylase (P-450c21) in 40 ovine fetal adrenals from 42 days of gestation until term (151 days). The genes for P-450(17 alpha) and P-450scc were expressed strongly in tissue from young (40-60 days) and old fetuses (120 days to term), but to a very minor degree in 90-120 day fetuses. P-450c21 showed a steady increase throughout gestation. In the morphologically immature an unzoned adrenal of the 40-50 day fetus there was some differentiation in gene expression, all cells containing P-450scc and P-450c21 but a few lacking P-450(17 alpha). Once morphological zonation had occurred (80 days), P-450(17 alpha) was confined to the fasciculata. After 120 days there was a radial maturation pattern of the fasciculata cells morphologically, adult-type cells first appearing at the medullary border. However, P-450(17 alpha) and P-450scc mRNAs were equally well expressed in all sections of the fasciculata. The conclusions were: 1) the previously demonstrated triphasic cortisol biosynthetic capacity of ovine fetal adrenals was correlated with the presence, absence, and reappearance of mRNAs P-450(17 alpha) and P-450scc; 2) morphological appearance of fetal adrenocortical cells and expression of three major steroidogenic enzyme genes were not correlated.