Leptin is essential for the establishment of pregnancy and appears to promote fetal growth but the mechanisms regulating fetal leptin exposure remain unclear. In rodents, indirect evidence suggests that fetal leptin is partly derived from the maternal circulation via transplacental passage. Indeed, the placenta expresses mRNA for Ob-Ra, one of the short forms of the leptin receptor (Ob-R_S) important in leptin transport, and this expression increases markedly in late pregnancy. Therefore, we determined the transplacental passage of maternal leptin to the fetus in the rat, and whether this transport increases near term in association with a rise in placental expression of Ob-R_S protein. Because of leptin's proposed role in promoting fetal growth, we also assessed the effect of glucocorticoid-induced fetal growth retardation on placental leptin transport. Anesthetized rats received a constant infusion of ¹²⁵I-leptin via a jugular cannula before and at days 16 and 22 of pregnancy (term = day 23); plasma samples were obtained at 10, 20, 40, 60, 80 and 100 min and fetuses and placentas were collected at the time of the final sample. The metabolic clearance rate (MCR) of leptin fell (P<0.01) from 3.08 ± 0.23 ml/min per kg in non-pregnant rats to 2.36 ± 0.13 ml/min per kg by day 22. Transplacental passage of ¹²⁵I-leptin, estimated from its concentration in the whole fetus relative to maternal plasma, increased 10-fold (P < 0.005) between days 16 and 22 of pregnancy. Over this same period Ob-R_S protein expression in the placental labyrinth zone increased by almost 2-fold. Transplacental leptin passage was reduced (P < 0.05) by 77% after maternal dexamethasone treatment, whereas suppression of endogenous glucocorticoid synthesis (by metyrapone) increased (P < 0.05) the transfer of maternal leptin to the fetus by 55%. These data show that transplacental passage of maternal leptin is a significant source of fetal leptin and increases markedly during late pregnancy. Consistent with the proposed role of leptin as a fetal growth factor, transplacental leptin passage is reduced in association with glucocorticoid-induced fetal growth retardation.