BACKGROUND Epidemiologic studies suggest that childbearing is an important contributor to the development of obesity in many women and that breastfeeding may be protective. Ghrelin and peptide YY (PYY) are gut hormones involved in appetite regulation and energy homeostasis and are biological neuroendocrine signals that potentially affect body weight and adiposity. OBJECTIVE This study evaluated whether fasting or postprandial ghrelin or PYY is different between lactating and nonlactating postpartum women matched for age, body weight, and adiposity. METHODS Ten postpartum lactating women (mean + or - SD: 28.1 + or - 4.9 y of age, 69.2 + or - 11.3 kg, 35.4 + or - 6.6% body fat) and 8 nonlactating women (28.8 + or - 7.6 y of age, 75.6 + or - 13.7 kg, 37.5 + or - 6.5% body fat) at 4-5 wk postpartum underwent measurements of body weight, body composition, and ghrelin and PYY responses to a standardized meal (350 kcal). Seven never-pregnant women served as control subjects (29.7 + or - 4.1 y of age, 60.4 + or - 4.8 kg, 25.5 + or - 2.0% body fat). RESULTS Ghrelin concentrations decreased, whereas PYY concentrations increased significantly (P < 0.05) in response to the meal, but fasting or meal-induced changes were not significantly different between lactating and nonlactating women. The fasting ghrelin concentration correlated with body mass index (r = -0.53, P < 0.05) and was significantly lower in postpartum than in control women (894.9 + or - 247.7 compared with 1316.9 + or - 241.0 pg/mL), even after adjustment for body mass index. CONCLUSIONS Our data do not support the notion that ghrelin, PYY, or both are plausible neuroendocrine signals that influence body weight regulation during lactation. They suggest, however, that ghrelin may change with increased adiposity in the postpartum state and may potentially play a role in body weight regulation after child birth.