Leptin is a 16 kDa protein mainly produced by adipose tissue in direct proportion to fat depot mass. Originally thought to be a satiety factor, leptin displays pleio-tropic activities. Both the structure of leptin and that of its receptor suggest that leptin might be classified as a cytokine. The secondary structure of leptin has similarities to the long-chain helical cytokine family, which includes IL-6. IL-11. CNTF, and LIF, and the leptin receptor is homologous to the gpl30 signal-transducing subunit of the IL-6-type cytokine receptors. Furthermore, leptin levels are acutely increased by inflammatory stimuli such as LPS and turpentine and by cytokines, indicating that leptin induction is part of the host response to inflammation. Defects in leptin production, such as observed in oh I oh mice, or in the long isoform of the leptin receptor (dhjdh mice and fa/fa rats) cause a complex syndrome characterized by severe obesity* infertility, and impaired immune responses.