Increased plasma levels of leptin appears to be a ubiquitous feature of pregnant mammals. The mechanisms by which leptin levels are increased may be species-specific, however, with some species upregulating adipose leptin production, and others expressing leptin in the placenta. Placental leptin expression was examined in representative species of the two most abundant mammalian orders, Rodentia and Chiroptera, and in cultured human choriocarcinoma (BeWo) cells. Leptin mRNA was expressed in BeWo cells, and in placentae of Myotis lucifugus (little brown bat), Eptesicus fuscus (big brown bat), and Rattus norvegicus (laboratory rat), but not of the common laboratory mouse Mus musculus. Cyclic AMP stimulated secretion of leptin from BeWo cells, and also stimulated leptin mRNA expression in the cells. In addition to adipose and placental tissue, leptin transcript in M. lucifugus was detectable in heart, spleen and liver, but was undetectable in lung, brain, and kidney. Hepatic expression was also observed in Eptesicus fuscus, but not in mice or rats, and did not appear to result from hepatic fat deposition. Leptin cDNA was cloned and sequenced from M. lucifugus placenta and shared up to 95% homology with other mammalian leptin cDNAs. It is concluded that: 1) placental leptin expression and secretion are species-specific traits; 2) placental leptin production represents one of three major mechanisms for achieving high circulating maternal leptin levels during pregnancy, the others being upregulation of adipose leptin production, and production of circulating leptin-binding proteins, and 3) hepatic leptin expression in pregnant insectivorous bats may be an adaptation resulting from the presence of extremely low amounts of subcutaneous fat during pregnancy and lactation in these species.