Leptin, the ob gene product, is considered as a signal involved in the regulation of energy stores through centrally mediated effects on ingestive behavior and metabolism. To investigate the relationships between appetite-related sensations and circulating leptin in humans, 12 healthy male volunteers were served two test lunches (1200 kcal, 38% carbohydrate, 50% fat, 12% protein) with comparable palatability but resulting in different postprandial hunger ratings, and plasma leptin concentrations were monitored during 8 h after meal ingestion. Whereas postprandial hunger ratings (assessed by visual analog scales) and plasma insulin patterns differed significantly between meals, no significant difference in postprandial plasma leptin concentrations was observed between the two meals. A moderate but significant increase in mean plasma leptin was found over time. We conclude that postprandial plasma leptin concentrations do not significantly differ between two meals inducing different effects on hunger subjective feelings. These data are in agreement with a role for leptin in the regulation of energy balance as a long-term adiposity-related signal rather than a short-term meal-related factor.