The biochemical and cellular mechanisms involved in the development and/or maintenance of morphine tolerance remain unclear. In the adult central nervous system (CNS) results are contradictory. For the neonate, a variety of drug induced deficits have been observed following prenatal addiction to opioids, although very little work on the biochemical and molecular level has been done. Therefore, the present study was carried out to investigate the effects of prenatal morphine treatment on the levels and expression of endogenous opioid peptides in brain regions of newborns. Dams were implanted with one morphine pellet (75 mg each) 1 week prior to the birth of pups. Changes in mRNA levels for the opioid peptides were determined by Northern blot analysis. Alterations in opioid peptide levels were determined by radioimmunoassays. Prenatal morphine treatment significantly increased proenkephalin mRNA levels and decreased met-enkephalin levels in striatum of newborns. These data are in contrast to what is observed in the adult CNS. These data indicate that prenatal morphine treatment may increase met-enkephalin release and/or cause inhibition at the level of translation. In addition, increased transcription may be necessary to maintain equilibrium in the system when there is an increase in met-enkephalin release.