Leptin is a 16-kDa protein produced mainly by adipocytes. Animal models demonstrate that leptin is required for control of bodyweight and reproduction, since mice defective in leptin or the leptin receptor are obese, hyperphagic insulin resistant and infertile. Our initial series of observations lead us to propose that leptin also had significant effects on human type I proinflammatory immune responses. In support of this hypothesis, leptin deficient mice are resistant to a wide range of autoimmune diseases and display features of immune deficiency. Subsequent work has confirmed that leptin has a pleiotrophic role on the immune response and can rightly be considered, both structurally and functionally, as a proinflammatory cytokine.