OBJECTIVE: We sought to evaluate the longitudinal changes in maternal serum leptin concentrations, body composition, and resting metabolic rate during pregnancy. STUDY DESIGN: Ten women were evaluated before pregnancy, in early pregnancy (12 to 14 weeks), and in late pregnancy (34 to 36 weeks). Leptin concentrations were measured by radioimmunoassay, body composition with hydrodensitometry with adjustment for total body water, and resting metabolic rate by use of indirect calorimetry. RESULTS: Using analysis of variance with repeated measures from pregravid to late pregnancy, a 66% increase (mean ± SD) was found in leptin concentrations (in nanograms per milliliter) (before pregnancy, 25.4 ± 19.9; in early pregnancy, 37.5 ± 26.2; and in late pregnancy, 38.4 ± 27.3, p = 0.003); a 9% increase in body fat (in kilograms) (before pregnancy, 29.4 ± 15.7; in early pregnancy, 28.7 ± 14.0; in late pregnancy, 31.4 ± 14.6; p = 0.04); a 28% increase in oxygen consumption (in milliliters of oxygen per minute) (before pregnancy, 221.2 ± 29.5; in early pregnancy, 230.4 ± 42.9; in late pregnancy, 285.3 ± 51.9; p < 0.0001); and a 9% increase in oxygen consumption (milliliters of oxygen per kilogram per minute) (before pregnancy, 3.02 ± 0.43; in early pregnancy, 3.05 ± 0.30; in late pregnancy, 3.31 ± 0.37, p = 0.002) with advancing gestation. A significant positive correlation was present between leptin and body fat before pregnancy (r = 0.90, p < 0.0001), in early pregnancy (r = 0.91, p < 0.0001), and in late pregnancy (r = 0.87, p = 0.0005) and between leptin and oxygen consumption before pregnancy (r = 0.80, p = 0.004), in early pregnancy (r = 0.92, p < 0.0001), and in late pregnancy (r = 0.62, p = 0.06). When oxygen consumption was adjusted for maternal and fetal tissue mass, a significant negative correlation was found between leptin and oxygen consumption before pregnancy (r = –0.96, p < 0.0001), in early pregnancy (r = –0.80, p = 0.0034), and in late pregnancy (r = –0.70, p = 0.02). CONCLUSION: We conclude that leptin increases significantly during early pregnancy before any major changes in body fat and resting metabolic rate. These data suggest that pregnancy represents a leptin-resistant state. (Am J Obstet Gynecol 1998;178:1010-5.)