We have read with much interest the article by Espinoza et al in which they reanalyzed data regarding high umbilical adenosine plasma level in fetuses from pregnancies coursing with preeclampsia that were presented in this Journal by the same group in 2 different articles in 1994 and 1996. We here intend to contribute to the discussion by incorporating ideas into the complex regulatory scenario that modulates the human umbilical adenosine level. In consequence with the proposal of Espinoza et al, the high extracellular level of adenosine that results from reduced expression and activity of human equilibrative nucleoside transporters 1 were described, for the first time, by our groups in primary cultures of human placental microvascular endothelial cells (hPMEC) from preeclampsia. We then hypothesized an abnormal adenosine handling by the fetoplacental circulation in this syndrome. However, this possibility raises the question of where adenosine is coming from? Accordingly, in hPMEC from preeclampsia, we recently have found altered adenosine-nucleotides catabolism compared with normal pregnancies (Escudero C, Sobrevia L, unpublished data). Nevertheless, whether these purines cross the placental barrier towards the maternal circulation and participate in the pathophysiologic condition of preeclampsia is unclear. However, it is intriguing that adenosine and purine metabolism is associated with high uric acid plasma levels in women who are given a diagnosis of preeclampsia; and adenosine triphosphate infusion generates a preeclampsia-like disease in rats. Another emerging question is what is adenosine controlling in the fetoplacental circulation? Since adenosine induces vasodilatation or vasoconstriction in several vascular beds (including the human placenta) and regulates angiogenesis, it is likely that a high adenosine level in the fetoplacental circulation in preeclampsia is an adaptive response that courses with placental angiogenesis in coordination with changes in maternal blood flow. This was proposed by our group in a review in 2009 and agrees with the study of Espinoza et al. However, because there is no literature that demonstrates a direct relationship among those effects, further studies to characterize the involved mechanisms are required. Thus, we certainly reinforce the importance of addressing adenosine roles in the pathophysiologic condition of maternal and fetal vascular dysfunction in preeclampsia and aim to encourage informed discussion in the field retouched by Espinoza et al in their recent review in this Journal.