To examine whether the activation of the renin system, which occurs during pregnancy, may be relevant for the development and the outcome of the fetus, we measured active and inactive renin throughout gestation in 29 women having a pregnancy defined as "high risk" because of a clinical history of hypertension, nephropathy, and unexplained abortions. In 23 of these women who delivered full-term infants with normal weight and status, we found that active renin increased progressively from early pregnancy until the end of the second trimester and then declined slightly thereafter. In contrast, in the remaining six women who had fetal complications consisting of either signs of distress requiring cesarean section or growth retardation, the increase in active renin failed to occur. In all women the levels of inactive renin were more elevated throughout gestation than those observed in nonpregnant women, and were higher, although not significantly, in women without fetal complications than in those with fetal complications. Thus, a blunted activation of the renin system during pregnancy is associated with alteration in fetal development and may possibly contribute to it.