To assess the impact of the macronutrient content of a meal on the postprandial leptin response and its relationship with postprandial satiety, 22 young healthy subjects (11 men and 11 women) were given, in a randomized order, an isoenergetic meal [carbohydrate (81%) or fat (79%)] or remained fasting. Blood sampling and hunger and satiety scores were collected hourly during 9 h after the meal. Spontaneous intake was measured at a buffet meal at 9 h postprandially. In both genders, leptin response was higher after the carbohydrate meal than after the fat meal and while fasting. In women, leptin levels were higher after the fat meal than while fasting. Leptin response was significantly correlated to insulin response (r = 0.51, P < 0.0001). Hunger and satiety ratings and subsequent energy intake were not different after carbohydrate or fat intake. In conclusion, a carbohydrate meal induces higher postprandial leptin levels than an isoenergetic fat meal. Short-term regulation of postprandial satiety and food intake is not influenced by circulating leptin.