Placental glucose transfer is facilitated by membrane transporter proteins of which Glut-1 is the predominant isoform. We examined the role of placental Glut-1 expression as a counter-regulatory mechanism in fetal overgrowth associated with fetal hyperglycemia and hyperinsulinemia. In a rat model, previously described, selective ablation of alternative fetuses by uterine artery branch ligation produced transient hyperglycemia and hyperinsulinemia in the survivors that resolved by term. This suggested that the placenta might respond to increased maternal glucose delivery with decreased expression of Glut-1 to reduce glucose transfer and restore fetal normoglycemia. Ligations were performed on gestational day 14 (term=21.5) and fetuses delivered by hysterotomy on day 20. Control fetuses were delivered at the same gestational age from non-instrumented mothers. Five litters from each group were studied and placental samples from each litter were used to extract protein and RNA (n=10). Glut-1 protein expression was measured by Western blotting and quantified by autoradiograph densitometry. Glut-1 mRNA was measured by reverse transcription with subsequent PCR amplification and quantification by phosphorimaging. Immunohistocytochemistry was performed on fixed placental samples to localize Glut-1. Results: Birthweights were higher in the selectively ligated litters (LGA) compared to controls (4.2± 0.1 vs 3.6 ± 0.1 grams, p<.05). Placental weights were not significantly different (.55±.02 vs.52±.02 grams). Pooled serum glucose and insulin concentrations were similar in both groups on day 20(5.4±.7 vs 5.2±.2 mmol/L, p=NS, and 22±1 vs 22±3 ng/mL, p=NS). Decreased expression of Glut-1 mRNA was noted in the LGA group(.39±.08 × control). However, expression of Glut-1 protein was not significantly decreased (.80±.25 × control). Immunohistochemistry revealed staining on the syncytiotrophoblastic membranes facing the maternal blood sinus and the fetal capillary. The intensity of staining was qualitatively similar in both groups. Conclusion: The placenta responds to increased maternal perfusion with decreased expression of Glut-1 message. However, this response is not associated with a significant decrease in Glut-1 protein expression. It seems likely that other mechanisms regulating uterine perfusion and fetal metabolism have greater physiologic importance.