The purpose of this study was to investigate the effects of leptin on human uterine contractility in vitro. Biopsies of human myometrium were obtained at elective cesarean section (n = 18). Dissected myometrial strips suspended under isometric conditions, undergoing spontaneous and oxytocin-induced contractions, were exposed to cumulative additions of leptin in the concentration range of 1 nmol/L to 1 micromol/L. Control strips were run simultaneously. Integrals of contractile activity were measured using the PowerLab hardware unit and Chart v3.6 software. Leptin exerted a potent and cumulative inhibitory effect on spontaneous and oxytocin-induced contractions compared to control strips. The mean maximal inhibition values were as follows: 46.794 +/- 5.133% (n = 6; P < .001) for spontaneous contractions and 42.323 +/- 3.692% (n = 6; P < .001) for oxytocin-induced contractions. There was an apparent reduction in both frequency and amplitude of contractions. This physiologic inhibitory effect of leptin on uterine contractility may play a role in the dysfunctional labor process associated with maternal obesity, and the resultant high cesarean section rates.