Ghrelin is a growth hormone and cortisol secretagogue that plays an important role in appetite and weight regulation. It is not known whether ghrelin is involved in the eating response to stress in humans. In the present study we examined the effects of psychologically induced stress on plasma ghrelin levels in patients with binge-eating disorder (BED) (n=8) and in healthy subjects of normal (n=8) or increased (n=8) body mass index (BMI). Volunteers were subjected to the standardized trier social stress test (TSST). Heart rate, blood pressure, serum cortisol, serum prolactin, and plasma ghrelin levels were measured throughout the test. In addition, subjects were requested to rate their feelings of anxiety, tension, urge to eat uncontrollably and desire to eat sweets by means of a visual analog scale both before and after the TSST. There was a significant rise in the systolic blood pressure (p=0.003) in the study population, reflecting induction of physiological changes by the psychological challenge. Basal ghrelin levels were higher in healthy normal weight (385.4±79pg/ml) than in obese (170.4±15.7pg/ml) subjects (p<0.033). Basal ghrelin levels in patients with BED (240±40.8pg/ml) were at an intermediate level between thin and healthy obese subjects, but this difference did not attain statistical significance. There were no differences in ghrelin levels throughout the test among the groups after correction for BMI, age and gender. A significant difference in the trend time of ghrelin was revealed when the three groups were analyzed according to their cortisol response to stress. Ghrelin levels increased in cortisol responders whereas no change or a decrease in ghrelin levels occurred in cortisol non-responders (p=0.038). Furthermore, a positive correlation was found between the change in ghrelin and the change in cortisol during TSST (r=0.444, p=0.029) but not between the change in ghrelin and the change in systolic blood pressure. The combined score of stress and anxiety was higher in subjects in the higher quartile of ghrelin response in comparison to the lower quartile both before (28.3±6.5 vs. 6.6±3.3, p=0.0077) and after (61.6±9 vs. 28.3±11.3, p=0.033) TSST. On the other hand, eating related scores did not differ according to quartiles of ghrelin response. Our findings indicate that a psychological stress may induce an increase in plasma ghrelin levels in humans, and that the post-stress induced urge for uncontrolled eating is not acutely modulated by stress related elevations in ghrelin levels. Furthermore, the stress induced increase in plasma ghrelin was associated with the acute response of serum cortisol to stress, but was independent of BMI or the presence of BED.