Interleukin-6 (IL-6) is one of the main proinflammatory mediators of hypertension and endothelial dysfunction in preeclampsia. In this study, we investigated the capacity of the preeclamptic placenta to secrete IL-6 and the effect of magnesium sulfate (MgSO(4)) on it. Placentas from normotensive (37-40 weeks) and preeclamptic (36-40 weeks) pregnancies were dually perfused for 6 h in the absence [normotensive (n = 3); preeclamptic (n = 4)] and presence [normotensive (n = 3); preeclamptic (n = 4)] of MgSO(4). Perfusate samples from the maternal and the fetal circulations were collected at each 30 min throughout the perfusion period and examined for IL-6 by enzyme-linked immunoassay. Statistical analysis was performed using the 2-way analysis of variance. In the absence of MgSO(4), IL-6 levels in the maternal and the fetal circulations of preeclamptic placentas (4.2 ± 1.3 and 0.9 ± 0.5 pg/mL/g cotyledon; respectively) were significantly higher, when compared with normotensive placentas (1.9 ± 0.5 and 0.2 ± 0.2 pg/mL/g cotyledon; respectively) (P < 0.05). Addition of MgSO(4) to the perfusate of normotensive placentas did not affect IL-6 secretion. However, exposure of preeclamptic placentas to MgSO(4) resulted in decreased IL-6 levels in the maternal circulations (1.7 ± 0.3 pg/mL/g cotyledon), when compared with the control group (P < 0.05). In the fetal circulation, the addition of MgSO(4) resulted only in a nonstatistical significant tendency toward decreased IL-6 levels, when compared with the control group. Our findings indicate that the perfused preeclamptic placenta secretes increased levels of IL-6 into the fetal and the maternal circulations and that MgSO(4) may normalize these increased secreted IL-6 levels.