The view that the adipocyte acts only as a passive storage site for energy in the form of triglyceride has been rendered obsolete by the discovery that adipocytes secrete a variety of metabolically active molecules. These molecules include free fatty acids, which decrease the rate of glucose oxidation by peripheral tissues; adipsin and other complement factors involved in host defense; tumor necrosis factor alpha, which may be an important determinant of insulin sensitivity; and angiotensinogen, which appears to promote terminal differentiation of preadipose to adipose cells. Leptin, a 167 amino acid polypeptide encoded by the obese gene, is a recently described adipocyte secretory product that communicates the status of the body's energy reserve to the central nervous system, apparently for the purpose of regulating body composition. Plasma leptin levels are exponentially related to total adipose mass. Daily injection of leptin into ob/ob mice leads to decreased food consumption and increased energy expenditure, both of which result in loss of adipose mass. Leptin-treated animals also have lower circulating insulin and glucose levels than pair fed controls. Finally, leptin corrects the infertility of ob/ob mice by restoring gonadotropin secretion to normal. These observations indicate that the adipocyte plays a key role in energy balance, insulin action, host defense, and reproduction, and suggest new approaches for understanding several important human diseases.