The ontogenic expression of proenkephalin A (ProEnk A) mRNA and phenylethanolamine N-methyltransferase (PNMT) mRNA was examined in the foetal sheep adrenal medulla by the use of specific oligodeoxyribonucleotide probes. Northern blot analysis of RNA extracts from foetal adrenals demonstrated that ProEnk A mRNA was expressed as early as 60 days of gestation, a time at which the foetal adrenal is not functionally innervated. In situ hybridization on sections of foetal adrenals revealed that at 110-140 days gestation ProEnk A mRNA was expressed in chromaffin cells at the outer margin of the adrenal medulla but at earlier stages of gestation (e.g. 95 days) appeared to be expressed homogeneously throughout the whole of the adrenal medulla. In comparison, PNMT mRNA was expressed preferentially in cells at the outer margin of the adrenal medulla from the earliest stage detectable. Both PNMT mRNA and ProEnk A mRNA co-localized in cells at the outer margin of foetal adrenal of late gestations (110-140 days), a similar pattern to that seen in the adult adrenal medulla. These results indicate that, as with adult animals, in foetuses of late gestation, adrenal enkephalins are co-stored within adrenaline cells. It is likely therefore that enkephalins are co-released from the foetal adrenal with adrenaline in response to intra-uterine stress.