Postnatal appetite control and body weight gain pattern is regulated by the balance between two major central neuropeptides, the orexigenic neuropeptide Y(NPY) and the anorexigenic corticotropin-releasing factor (CRF). To determine whether this neuropeptide balance can be perturbed in-utero by metabolic derangements, we examined the effect of 24 hour-uteroplacental insufficiency in a maternal uterine artery ligation rat model associated with fetal growth restriction, hypoglycemia, and hypoinsulinemia (IUGR). In the IUGR (n=10) and sham operated age matched controls (CON; n=10), 20d gestation fetal brain NPY and CRF mRNA levels were quantitated by Northern blot analysis and standardized to 18S rRNA. The NPY peptide levels were determined in brain extracts by radioimmunoassay using a rabbit anti-rat NPY IgG. A two-fold increase in NPY mRNA (0.8 kb) levels was observed in fetal IUGR when compared to CON (p < 0.05). In contrast no change in fetal CRF mRNA (1.4 kb) levels was noted. While fetal brain NPY peptide concentrations did not differ, examination of the 1d old neonatal progeny (n=4) demonstrated a two-fold increase in the IUGR progeny brain NPY peptide levels when compared to age-matched CON (p <0.05). Immunohistochemical analysis revealed the presence of NPY immunoreactivity within scattered neuronal cell bodies and processes within the hippocampal/cerebral cortical regions, with a predominant presence in nerve terminals of the hypothalamic paraventricular nucleus. We conclude that 1] IUGR associated with fetal hypoglycemia and hypoinsulinemia alters the ratio between hypothalamic NPYand CRF mRNAs and 2] sets the stage for elevated postnatal brain NPY peptide concentrations. We speculate that this in-utero pretranslational increase in hypothalamic NPY concentrations preprograms the postnatal animal towards hyperphagia to compensate for the in-utero metabolically deprived state.