The aim of this study was to investigate the ontogeny of serum leptin concentrations during the second half of gestation and at birth in small for gestational age and normal fetuses and newborns. Serum leptin concentrations were measured in arterial cord blood of fetuses (n = 79) and newborns (n = 132), with or without intrauterine growth retardation, at 18-42 weeks gestation. Serum leptin was detectable in fetal cord blood in all subjects as early as 18 weeks gestation. Leptin levels dramatically increased after 34 weeks gestation. In newborns, serum leptin concentrations were positively correlated with body weight (P < 0.001) and body mass index (P < 0.001). Newborns with intrauterine growth retardation had significantly lower serum leptin values (P < 0.001) than those with normal growth, and leptin levels were only positively correlated with body mass index (P < 0.001). These results suggest that the development of adipose tissue and the accumulation of fat mass are the major determinants of fetal and neonatal serum leptin levels. In addition, a gender difference, with higher leptin concentrations in female fetuses, was observed during the last weeks of gestation and was confirmed at birth regardless of growth status, suggesting that a sexual dimorphism already exists in utero.