Aging is often associated with overweight and obesity. There exists a long-standing debate about whether meal pattern also contributes to the development of obesity. The orexigenic hormone ghrelin regulates appetite and satiety by activating its receptor, growth hormone secretagogue receptor (GHS-R). In mice, circulating ghrelin concentrations and brain GHS-R expression were shown to increase with aging. To assess whether GHS-R regulates feeding pattern during aging, we studied meal patterns for the following cohorts of male mice fed a normal unpurified diet: 1) 3-4 mo, young wild-type (WT) mice; 2) 3-4 mo, young Ghsr-null (Ghsr) mice; 3) 12-14 mo, middle-aged WT (WT-M) mice; 4) 12-14 mo, middle-aged Ghsr (Ghsr-M) mice; 5) 24-26 mo, old WT (WT-O) mice; and 6) 24-26 mo, old Ghsr (Ghsr-O) mice. Although the total daily food intake of Ghsr mice was similar to that of WT controls, Ghsr-M and Ghsr-O mice had 9% (P = 0.07) and 16% (P < 0.05) less body weight compared with WT-M and WT-O mice, respectively, primarily due to reduced fat mass (P < 0.05, WT-M vs. Ghsr-M and WT-O vs. Ghsr-O). Intriguingly, Ghsr-M mice ate largermeals (on average, Ghsr-M mice ate 0.117g/meal andWT-Mmice ate 0.080 g/meal; P < 0.01) and took a longer time to eat (Ghsr-M, 196.0 s andWT-M, 128.9 s; P < 0.01), but ate less frequently (Ghsr-M, 31.0 times/d and WT-M, 42.3 times/d; P < 0.05) than WT-M controls. In addition, we found that expression of hypothalamic orexigenic peptides, neuropeptide Y (NPY) and agouti-related peptide (AgRP), was relatively lower in aged WT mice (P = 0.09 for NPY and P = 0.06 for AgRP), but anorexic peptide pro-opiomelanocortin (POMC) expression remained unchanged between theWT age groups. Interestingly, old Ghsr mice had greater hypothalamic NPY expression (102% higher; P<0.05) and AgRP expression (P = 0.07) but significantly lower POMC expression (P < 0.05) when compared with age-matchedWT-O controls. Thus, our results indicate that GHS-R plays an important role in the regulation ofmeal pattern and that GHS-R ablation maymodulate feeding behavior through the regulation of hypothalamic neuropeptides. Our results collectively suggest that ghrelin receptor antagonism may have a beneficial effect on metabolism during aging.