We previously demonstrated that leptin amplified feeding inhibition and neural activation produced by either cholecystokinin (CCK) or intragastric preloads, suggesting that leptin may increase the efficacy of gastrointestinal meal-related signals. To determine whether leptin would similarly potentiate the feeding inhibitory actions of another putative satiety peptide, we evaluated the effect of third ventricular leptin administration on food intake and c-Fos activation in response to systemically administered bombesin (BN). Leptin (3.5 µg) was administered 1 h prior to either 0.9% saline or BN (0.32 and 1.0 nmol/kg) followed by 30 min access to Ensure liquid diet. While neither leptin nor 0.32 nmol/kg BN alone suppressed Ensure intake, the combination reduced intake by 28%. The higher BN dose (1.0 nmol/kg) produced a significant suppression by itself but was further enhanced in the presence of leptin. Consistent with the behavioral results, c-Fos activation in the nucleus of the solitary (NTS) was increased by combined dosages of leptin and 0.32 nmol/kg BN beyond the individual response to either peptide. In the presence of leptin, BN produced a 3.4 to 5.2-fold increase in the number of fos-positive cells in the NTS compared to when BN was given alone. These data provide further support for the hypothesis that the effect of leptin on food intake may be mediated, in part, by modulating meal-related satiety signals.