The response of brain tryptophan concentration and serotonin synthesis to the ingestion of two sequential meals was examined in rats. Fasted rats ingested a carbohydrate meal followed 2 h later by a protein-containing meal and were examined 2 or 4 h after the first meal. Other rats ingested a protein meal first, followed by a carbohydrate meal. When the carbohydrate meal was fed first, brain tryptophan concentrations and serotonin synthesis increased at 2 h; these changes were reversed at 4 h if the second meal contained protein. When the protein meal was fed first, there were no changes in brain tryptophan or serotonin at 2 h, and a second carbohydrate meal at 2 h did not raise brain tryptophan or serotonin 2 h later. Carbohydrate ingestion 3 h after a protein meal, however, did raise brain tryptophan and serotonin 2 h later. Brain tryptophan concentrations and serotonin synthesis are thus responsive to the sequential ingestion of protein and carbohydrate meals if there is a sufficient interval between meals.