Context: Inadequate trophoblast invasion and spiral artery remodeling leading to poor placental perfusion are believed to underlie the pregnancy pathologies, preeclampsia (PE) and intrauterine growth restriction (IUGR). Main Objective: To investigate HIF- and downstream genes (VEGF receptor-1) Flt-1 and (soluble) sFlt-1 proteins in IUGR placentas. Design: Placentas from normal pregnant (NP, n=18), PE (n=18) and IUGR (n=10) patients were investigated. Normotensive patients with IUGR delivered babies 37 weeks of gestation with birth weights <10% and asymmetrical growth. HIF-1 and -2, Flt-1 and sFlt-1 protein and mRNA were assessed by Western and Northern analyses, respectively. The results are expressed as ratios of the densitometric values for each pair of pathologic and normal placentas, a ratio of 1.0 indicating no difference. Results: Comparable to our earlier studies, the PE/NP ratios for HIF-1, -2, and Flt proteins were 1.5-2.0 (all p < 0.01 vs 1.0). Unexpectedly, the IUGR/NP ratios for HIF-1 and -2proteins were 1.03 + 0.07 and 0.96 + 0.16, respectively, and for Flt and sFlt, 1.14 ± 0.15 and 0.95 ± 0.12, respectively (all p = NS vs 1.0). HIF- mRNA was comparable between abnormal and normal placentas. Conclusion: In contrast to PE, HIF- proteins and regulated genes are not increased in placentas from normotensive pregnant women delivering small, asymmetrically grown babies 37 weeks of gestation. The lack of HIF-induction is not due to insufficient HIF- mRNA for protein synthesis. Thus, the placentas from women with PE and late IUGR are fundamentally different at the molecular level.