- Objective: To evaluate the effect of pathological placental conditions such as intrauterine growth restriction (IUGR) or exposure to angiotensin II (AII) on TNF-α secretion in the vasculature of isolated human placental cotyledons. Study design: Isolated placental cotyledons from 10 normal and four intrauterine growth restricted fetuses were dually perfused. Perfusate samples from the fetal circulation were collected every 30 min during 120 min. TNF-α levels in the fetal–placental perfusate were evaluated using specific commercial ELISA kits. In three additional normal placentae, bolus injections of angiotensin II (10 −9 –10 −4 mol/l) were given into the fetal–placental circulation and perfusate samples were collected. Statistical significance of difference TNF-α levels between different conditions was determined by analysis of variance (ANOVA) and paired t -test. Results: TNF-α levels were significantly higher in the perfusate of IUGR placentae as compared with normal placentae after 120 min of perfusion (mean 410±121 vs. 39±14 pg/ml, P =0.005). There was a significant dose-dependent increase in TNF-α levels in the placental perfusate after a bolus injection of AII 66 pg/ml with AII 10 −9 mol/l vs. 97 pg/ml with AII 10 −5 mol/l ( P =0.004), respectively. Conclusions: Placental pathology related to condition IUGR might induce the secretion of proinflammatory cytokines such as TNF-α, which may enhance the vasoconstriction of the fetal placental vascular bed.