Leptin and insulin are secreted into the maternal and to a lesser extent into the fetal bloodstream where they act as placental signals and nourish the fetus, making them possible candidates for the endocrine control of the placenta. We investigated differences in leptin (LR) and insulin receptors (IR) expression in normal and disturbed first trimester human pregnancy at protein level by immunohistochemistry and at mRNA level by real-time reverse transcriptase-polymerase chain reaction (TaqMan). Highest expression of LR and IR was present in villous (VT) and extravillous trophoblasts (EVT). In hydatidiform mole trophoblasts, significantly higher LR and IR expression was observed when compared with normal pregnancy. In addition, LR and IR were also expressed in glandular epithelial cells of the decidua, again to the highest extent in hydatidiform mole when compared with normal pregnancy. With regard to abortive placentas, significant differences were also present when compared with normal first trimester placenta in the expression of LR and IR in VT, EVT and in glandular epithelial cells of the decidua. Results at protein expression of LR and IR were confirmed at mRNA level. The majority of IR and LR are expressed on structures that are currently assumed to drive placental growth. LR and IR are strongly up-regulated in placentas of hydatidiform mole and abortion. Our findings may suggest IR and LR as possible new candidates for the endocrine control of human pregnancy.