Leptin is a hormone secreted from adipocytes and trophoblasts which might influence energy metabolism during gestation. In this study we evaluated the course of free and bound leptin levels in 22 healthy pregnant women and compared these values to those in non-pregnant women matched for body mass index (BMI) and age. Serum concentrations of both leptin components and plasma levels of estradiol, progesterone, insulin, non-esterified fatty acids and glucose were measured at each trimester. The BMI increased from the first to the second trimester (22.8 +/- 3.1 and 24.7 +/- 2.9, respectively; p < 0.05) and remained stable thereafter (third trimester 25.3 +/- 2.9 kg/m2). Free leptin and bound leptin did not differ between patients and controls in the first trimester of pregnancy. Free leptin levels increased from the first (122 (60)) to the second trimester (181 (60) pmol/l; p < 0.05) and remained constant (third trimester 181 (76) pmol/l; difference between second and third trimesters, NS). Bound leptin increased from the second (0.43 (0.16)) to the third trimester (0.57 (0.21) nmol/l; p < 0.05). Only bound leptin was higher in the patient group in the third trimester compared to controls (p < 0.01). Our findings of a shift in free leptin to bound leptin in late pregnancy may indicate different physiological roles for both components. Free leptin may reflect maternal fat stores, whereas bound leptin may regulate maternal metabolism via central effects on food intake and energy expenditure.