Leptin is an adipocyte-derived product of the ob gene thought to be involved in the regulation of eating. Receptors for leptin have been found in multiple regions in the brain. In particular, hypothalamic receptors seem to be of fundamental importance for the biological effects of leptin. However, the association of leptin with cerebral function in humans has not been studied. Therefore, in order to assess the possible functional relationships between leptin and cerebral activity in humans, simultaneous serum leptin and regional cerebral blood flow (rCBF) measurements were made in 10 obese [BMI 33.5 (29.3–39.1) kg/m<sup>2</sup>] and 12 normal-weight [BMI 22.2 (20.3–24.6) kg/m<sup>2</sup>] women during exposure to food. The rCBF measurements were performed by <sup>99m</sup>Tc-ethyl-cysteine-dimer single photon emission computed tomography. A strong inverse association was observed between the leptin and rCBF of hypothalamus during the exposure to food in the obese (r = –0.73, p = 0.02, n = 10), but not in the normal-weight subjects (r = 0.22, p = 0.48, n = 12). This suggests that the association of leptin with cerebral activity could be different in obese and normal-weight women; depressed activity of hypothalamic neurones in response to the high peripheral leptin concentration could be postulated to occur in obese women during exposure to food.