Billions of birds migrate long distances to either reach breeding areas or to spend the winter at more benign places. On migration, most passerines frequently stop over to rest and replenish their fuel reserves. To date, we know little regarding how they decide that they are ready to continue their journey. What physiological signals tell a bird's brain that its fuel reserves are sufficient to resume migration? A network of hormones regulates food intake and body mass in vertebrates, including the recently discovered peptide hormone, ghrelin. Here, we show that ghrelin reflects body condition and influences migratory behavior of wild birds. We measured ghrelin levels of wild garden warblers (Sylvia borin) captured at a stopover site. Further, we manipulated blood concentrations of ghrelin to test its effects on food intake and migratory restlessness. We found that acylated ghrelin concentrations of garden warblers with larger fat scores were higher than those of birds without fat stores. Further, injections of unacylated ghrelin decreased food intake and increased migratory restlessness. These results represent experimental evidence that appetite-regulating hormones control migratory behavior. Our study lays a milestone in migration physiology because it provides the missing link between ecologically dependent factors such as condition and timing of migration. In addition, it offers insights in the regulation of the hormonal system controlling food intake and energy stores in vertebrates, whose disruption causes eating disorders and obesity.bird migration | ghrelin | migratory restlessness | food intake | stopover E very year, billions of birds migrate long distances to either reach areas offering favorable wintering conditions or breeding grounds that thrive with food during the reproductive season. For most small passerines, migration involves frequent stopovers to rest and refuel. During stopover, birds are exposed to fluctuating environmental conditions, including weather and food, which influence the duration of their stay. However, the final decision to resume migration depends on the interplay between environmental conditions, the endogenous program, and the physiological condition of an individual. Theory predicts that stopover decisions depend on amount and rate of deposition of energy stores (1, 2), and empirical findings have confirmed this hypothesis (3-12). The big and yet unanswered question is, How do birds know that they are ready to depart? That is, which physiological signals tell the brain that the fuel reserves are sufficient to resume migration? This link that connects physiological condition and brain is still unknown.Previous work has shown that fat stores are the best predictor for migratory disposition and stopover duration: Birds with larger subcutaneous (s.c.) fat stores show more migratory restlessness in captivity (8,10,13,14), stay shorter times at stopover sites (9, 11), and migrate faster (12). Because birds fuel their migratory flights primarily through fatty acid metabolism (15-...