The effects of specific nutritional factors on ghrelin secretion have not been investigated in humans. Therefore, we assessed ghrelin responses to a high-carbohydrate meal (1217 kcal with 77% carbohydrates, 10% protein, and 13% lipids) and to an isocaloric high-fat meal (15% carbohydrates, 10% proteins, and 75% lipids) in 14 nonobese healthy women. Eleven subjects also rated their hunger feelings on visual analog scales. Circulating ghrelin abruptly fell after both meals, but, after the carbohydrate meal, its maximum percent decrease was significantly greater than after the fat meal (P = 0.02). Plasma insulin and glucose levels rose after the meals, but their increases were significantly higher after the carbohydrate meal than after the fat meal. No significant change was observed in circulating leptin after both meals. Moreover, compared with the fat meal, the carbohydrate meal had a significantly greater suppressant effect on hunger feelings. Plasma ghrelin changes were significantly associated with hunger changes (P < 0.007). These findings show that circulating ghrelin is differently suppressed by diet manipulations. The mechanisms responsible for such a phenomenon and its possible implication in the physiology of human satiety remain to be elucidated.