Bombesin (BN)-like peptides have been implicated in the regulation of ingestive behavior. The main objective of the present study was to monitor the dynamics of central BN-like peptide release in relationship to spontaneous meal ingestion and termination. Peptide level fluctuations were determined using in vivo push-pull perfusion of the hypothalamic paraventricular nucleus (PVN) and off PVN sites, combined with ex vivo radioimmunoassay. Analysis across all meals revealed significant differences between preprandial, prandial and postprandial extracellular BN-like immunoreactivity (BLI) at the anterior aspect of the PVN, with about a 3-fold diminution during a meal as compared to before or after a meal. Meal-related fluctuations were not detected at more distal hypothalamic sites or at sites within the caudate nucleus. When the analysis was restricted exclusively to the first meal after dark onset, a similar pattern of change in the interstitial levels of PVN BLI was generally observed; levels being higher preprandially as compared to the prandially (albeit by a smaller magnitude), and the termination of the first meal being accompanied by a robust (about 3-fold) increase in BLI. This is the first demonstration of site specific in vivo release of BN-like peptides in relation to feeding status and it further supports the physiological role of this family of peptides in the regulation of food intake.