Blood glucose regulation in the fasting and fed states has important implications for health. In addition, the ability to maintain normal blood glucose homeostasis may be an important determinant of an individual's capacity to regulate food intake. We tested the hypothesis that aging is associated with an impairment in the ability to maintain normal blood glucose homeostasis following the consumption of large meals but not small ones, a factor that could help to explain age-related impairments in the control of food intake and energy regulation. The subjects were eight healthy younger women (25 +/- 2 years, SD) and eight healthy older women (72 +/- 2 years) with normal body weight and glucose tolerance. Following a 36-h period when diet and physical activity were controlled, subjects consumed test meals containing 0, 1046, 2092, and 4184 kJ (simulating extended fasting, and consumption of a snack, a small meal, and a moderately large meal), with 35% of energy from fat, 48% from carbohydrate, and 17% from protein. Each subject consumed each of the test meals on a separate occasion. Serial blood samples were collected at baseline and during 5 h after consumption of the meals. Measurements were made of circulating glucose, insulin, glucagon, free fatty acids, and triglycerides. There was no significant difference between young and older women in their hormone and metabolite responses to fasting and consumption of the 1046-kJ meal. However, following consumption of 2092 and 4148 kJ, older individuals showed exaggerated responses and a delayed return to premeal values for glucose (p = .023), insulin (p = .010), triglycerides (p = .023), and the ratio of insulin to glucagon (p = .026). In conclusion, these results suggest an impairment in the hormonal and metabolite responses to large meals in older women.