Background: Leptin is a growth factor for the fetus. The sources for maternal and fetal leptin plasma levels are the adipose tissue and the placenta. Placental leptin release elevates maternal leptin levels only about 15%. We hypothesize that activated adipose tissue is an additional source for the high leptin levels in pregnancy. However it is further not clear if maternal leptin reaches the fetal circulation and supports fetal growth by that way. Aim of the study: (1) Do maternal leptin arrive the fetal circulation and (2) is maternal adipose tissue leptin production activated during pregnancy ?Methods: Placentas and adipose tissue was obtained after written informed consent of the patients. (1) Dual in vitro perfusion of isolated cotyledons (n=7) for 3h. Addition of 125-I-leptin and unlabeled leptin (1+3, 22 ng/ml total leptin) to the maternal circulation. Control of vitality and integrity by measurement of glucose consumption, lactate production, creatinine- and antipyrin transfer. (2) Sampling of subcutaneous maternal adipose tissue during cesarean sections (n=10, no gestational pathology) and during other gynecological surgery (n=10, age matched, no malignancies). Measurement of leptin mRNA using Taqman real time PCR.Results: (1) Materno-fetal transfer rate of the labeled leptin was 4,5 ± 1,4% of the initial concentration. Permeability of 125-I-leptin accounted for 0,04 ± 0,02 ml min-1 g-1, and was 1,3 ± 0,1 ml min-1 g-1 normalized to creatinine transfer. Existence of free 125-iodine was excluded by comparison of dialysated and undialysated fetal perfusion medium. (2) Leptin mRNA was significant higher in adipose tissue of pregnant women than in the control group (1,0 ± 0,5 v. 0,5 ± 0,4 rel. Units; p<0,05)Conclusion: (1) We could show first, that leptin from the maternal circulation passes the placenta and enters the fetal blood. There seems to be an active transplacental transport from the maternal to the fetal circulation, due to molecular weight and calculated permeability. (2) Maternal adipose tissue leptin production is activated during pregnancy. A basic leptin supply in the beginning of fetal development seems to be guaranteed by the placenta and maternal adipose tissue and was supplemented by the own leptin production of the fetus during further maturation and growth.