OBJECTIVE: To investigate whether acute feeding induces changes in circulating leptin levels in humans and whether these changes vary according to nycthemeral cycle. METHODS: First experiment. Eighteen male subjects were given a fatty meal at 08.00 h. Blood sampling was performed for 10 h following this meal. Second experiment. Thirteen male subjects were given either a mixed meal or remained fasting either at night (starting at 01.00 h) or during the day (starting at 13.00 h). Blood samples were drawn every hour for a period of 8 h. RESULTS: First experiment. Serum leptin levels increased progressively from a mean (s.d.) baseline of 3.8 +/- 2.2 ng/ml to a value of 4.5 +/- 2.7 ng/ml (P < 0.01) 8 h after the fatty meal. Second experiment. During the day, serum leptin levels increased progressively from 2.65 +/- 1.7 to 3.34 +/- 2.2 ng/ml (P < 0.001) 6 h after the test-meal and decreased from 2.68 +/- 1.5 to 1.9 +/- 1.1 ng/ml (P < 0.001) 8 h after the beginning of the fasting experiment. Similar results were obtained at night. No statistically significant differences in leptin levels were observed between day and night sessions in response to feeding (mean area under the curve: 3.0 +/- 4.1 vs 4.1 +/- 4.1 ng/ml) and fasting (-2.9 +/- 2.2 vs -1.5 +/- 2.2 ng/ml). CONCLUSION: In two independent experiments, human serum leptin levels increase following food intake. This response is not influenced by nycthemeral cycle.