Leptin, a hormone secreted from adipose tissue, plays an important role in reproductive physiology. It has been shown to stimulate the reproductive system by rescuing the sterility of leptindeficient mice and advancing the onset of puberty in normal mice. Although leptin is not critical for the biology of pregnancy in mice, its ability to reduce food intake is blunted in midgestation suggesting that late pregnancy may be a leptin-resistant state. Modifier genes originating from theBalb/cJ genetic background profoundly alter the sterile-obese phenotype ofob/ob mice by reducing their obesity and stimulating their reproductive system despite the absence of leptin. The mechanism of leptin's action on the reproductive system remains to be determined but is likely to be mediated by multiple factors.