Opioid peptides are known to play a role in the function of the mammalian cardiovascular system in the newborn. To learn about mechanisms underlying the morphogenesis of the developing vasculature and the principles contributing to the organization and maintenance of adult blood vessels, we have investigated the expression of the opioid growth factor (OGF), [Met5]-enkephalin, and its receptor, zeta. Moreover, gene expression for preproenkephalin mRNA, which encodes OGF, was studied to determine the source(s) of this inhibitory growth factor. By using immunocytochemistry, both OGF and the zeta opioid receptor were detected at embryonic day (E) 16 in the mesenchymal cells of the aortic wall. Staining appeared to be abundant in endothelial cells, smooth muscle cells, and fibroblasts at E20 and in the neonate. Immunoreactivity was noted to decrease progressively from day 5 to 10, but by weaning (day 21) and continuing into adulthood intense staining for both the peptide and receptor were observed. Preproenkephalin mRNA was detected throughout the aortic wall at E16, and the number of silver grains increased up today. Message was progressively reduced at days 5, 10, and 21, but signal in the adult aorta was comparable to that observed at day 5. These results indicate that components related to an endogenous opioid system regulating growth are present in the embryo, display a distinct spatial and temporal pattern of ontogeny, and persist into adulthood. In addition, these data indicate that OGF is an autocrine produced growth factor that is related to the emergence of vascular architecture and the maintenance of homeostasis in blood vessels.