This study was intended for the investigation of the effects of chronic injections of leptin for 7 days on food intake and hypothalamic neurotensin (NT). Leptin treatment significantly reduced food intake [144.3+/-2.5 g (L) vs. 156.7+/-2.5 g (C); P=0. 002] and body weight gain [23.7 g+/-1.0 g (L) vs. 31.5+/-1.3 g (C); P=0.003]. NT concentration was lower in the lateral hypothalamus (LH) of leptin-treated rats than in the control ad libitum fed rats (-30%; P<0.05). The same diminution was observed in pair-fed rats (-27%; P<0.05). This diminution was therefore related to the decrease in food intake rather than to a direct effect of leptin. As the LH was the only area where NT was modified, it appears that among the hypothalamic nuclei involved in the regulation of feeding behavior it is the most sensitive area to a low energy depletion. Therefore, it might play a specific role in triggering the mechanisms necessary to restore body weight and/or energy balance.