Angiotensin II (Ang II) and apelin have opposing actions in the regulation of blood pressure, vascular tone and angiogenesis, factors known to be important in pregnancy. Chorionic villi (CV) are essential for the transport of oxygen and metabolites in the maternal-fetal interface. Previous studies from our group demonstrated the upregulation of Ang II in the CV of preeclamptic women. Since the interaction between Ang II and apelin have been suggested in the cardiovascular system, we determined whether Ang II alters the release of apelin from the placental CV obtained from normotensive pregnant (NP) and preeclamptic (PRE) women. We also established whether Ang-(1-7) influences apelin release from the same set of tissue samples. CV were dissected from the placental tissue, washed and incubated for 0, 2 and 16 hours in DMEM/F12 media with or without Ang II (1 nM and 1 μM) or Ang-(1-7) (1 nM and 1 μM) under controlled O2 and CO2 tensions. The unstimulated release of apelin measured by a competitive radioimmunoassay was significantly reduced in the conditioned media from PRE compared to NP chorionic villi at 2 hrs (PRE: 181.1 ± 31 vs. NP: 309.5 ± 51.4 pg/ml, p<0.05). There was a significant increase in apelin release from both NP (267.8 ± 34.8 vs. baseline: 118.4 ± 27.3 pg/ml, p<0.01) and PRE (293.5 ± 25.8 vs. baseline: 122.6 ± 24.8 pg/ml, p<0.01) CV at 16 hours. Ang II or Ang-(1-7) inhibited the release of apelin from CV of the NP (p<0.05) but not of PRE at 2 hours. At 16 hours, however, Ang II or Ang-(1-7) inhibited the release of apelin from both NP and PRE villi (p<0.05). Immunostaining revealed the predominant localization of apelin receptor to syncytiotrophoblasts and fetal vascular cells of CV - areas associated with AT1 receptor localization. Our data showing a negative influence of Ang II on apelin release from chorionic villi suggest an opposing interaction between these peptides in the human placental tissue. Reduced apelin activity would remove its counter-regulatory actions on Ang II-induced endothelial dysfunction, increased vascular resistance, and inflammation - abnormalities which precede and sustain preeclampsia. A surprising inhibitory effect of Ang-(1-7) on apelin suggests a complex regulation of apelin within the RAS.