The effect of insulin on glucose uptake, transfer, and metabolism was investigated in the human placenta perfused in vitro. Insulin concentrations in maternal perfusion medium were varied from 0-1200 microU/ml, whereas the glucose concentration was kept constant in maternal and fetal perfusion media. Despite significant uptake of insulin by the perfused placenta, neither glucose uptake and transfer nor lactate release were significantly modified during a 1-h insulin perfusion. The MCR of insulin by the placenta was 0.29 +/- 0.03 (+/- SEM) ml/min X g at physiological insulin levels. These data suggest that placental glucose transport and metabolism are insensitive to maternal plasma insulin variations and that the low clearance rate of insulin by the placenta is not a major determinant of maternal insulin adjustments during pregnancy.