Leptin, a hormone produced by adipose tissue and the placenta, is enhanced in the maternal circulation throughout pregnancy in both the human and the baboon ( Papio sp.), a proven nonhuman primate model for the study of human pregnancy. The presence of both leptin and its receptor in the fetus implies a role for the polypeptide as a regulator of in utero development, although localization in the placental trophoblast may relate to autocrine and/or paracrine regulatory functions in this important endocrine tissue. Although regulatory mechanisms remain incompletely defined, it has been suggested that cross talk occurs between the fetus, placenta, and maternal adipose stores. Placental estrogen, which is present in increasing concentrations with advancing gestation, is suggested to influence leptin synthesis in a tissue- and cell type-specific fashion. In this capacity, cellular hypoxia, diabetes, and preeclampsia are conditions that appear to be intimately linked to leptin dynamics. A better understanding of regulatory mechanisms will have direct clinical significance, as leptin has been proposed to impact on those causes of human perinatal morbidity and mortality that are associated with anomalies of fetal maturity and development, general conceptus growth, trophoblast endocrinology, and placental sufficiency.