Orexin A is produced in caudal lateral, posterior, perifornical and dorsomedial hypothalamic areas. Orexin A in the rostro-dorsal lateral hypothalamic area (rLHa) stimulates feeding and activates several feeding-regulatory brain areas. We hypothesized that aging diminishes feeding and cFos-immunoreactivity (cFos-ir; marker of neuronal activation) response to orexin A. Young (3 mo.), middle-aged (12 mo.) and old (24 mo.) male Fischer F/344 rLHacannulated rats were injected with orexin A (0.5, 1 and 2 nmol). Food intake was measured at 1, 2 and 4 h. C-Fos-ir in hypothalamic, limbic and hindbrain regions was measured in 2 additional sets of rLHa-orexin A injected rats; one set sacrificed at 1 h after injection, the other set at 2 h. In a separate study, orexin A effects on feeding and cFos-ir were measured in 6 mo. rats. Orexin A significantly elevated feeding in 3 mo., 6 mo. and 12 mo. rats in the 0-1 and 1-2 time intervals, whereas in old rats this was significant in the 1-2 h time interval only. At 1 h, 6-8 (of 14) brain areas showed elevated cFos-ir in response to orexin A in 3 and 6 mo. rats, but 24 mo. rats exhibited attenuated or absent cFos-ir response in all brain regions except the hypothalamic paraventricular nucleus (PVN) and rostral nucleus of the solitary tract (rNTS). Orexin A did not elevate cFos-ir in 3 mo. rats at 2 h following injection, whereas the PVN and mediodorsal thalamic nucleus (MD) showed elevated cFos-ir at 2 h in 24 mo. rats. These data suggest that delayed and diminished feeding responses in old animals may be due to ineffective neural signaling, and implicate the orexin A network as one feeding system affected by aging.