The gut hormone ghrelin is involved in feeding behaviour. It increases appetite and food intake when administered by intravenous infusion to subjects of normal weight. Ghrelin levels are often lower in obese than lean individuals and whether responsiveness to ghrelin differs in lean and obese people is not known. We investigated whether obese human subjects are sensitive to the effects of ghrelin. Approval of the local ethics committee was obtained. We examined the effects of intravenous infusions of ghrelin at 5.0 pmol/kg/min and 1.0 pmol/kg/min in 12 healthy lean subjects (mean BMI 20.5 plus/minus 0.17 kg/m2) and 12 healthy obese subjects (mean BMI 31.9 plus/minus 1.02 kg/m2), in a randomized, double-blind, placebo-controlled study. Ghrelin infusion lasted 75 minutes with a buffet meal served at 45 minutes. Low-dose infusion of ghrelin significantly increased ad libitum energy intake at the meal in the obese group only (mean increase 36.6 plus/minus 9.4%, p<0.01.) High dose ghrelin infusion increased energy intake in both groups (mean increase 20.1 plus/minus 10.6% in the lean and 70.1 plus/minus 15.5% in the obese, p<0.01 in both cases.) In the obese group the scoring of palatability of food was increased by 17.5 plus/minus 7.4% with low-dose ghrelin and 21.3 plus/minus 8.7% with high-dose ghrelin, compared to saline (p=0.04 in both cases.) No significant change in palatability was seen in the lean group. In addition, the growth hormone response in the obese group is blunted at both doses of ghrelin administered. Obese people are sensitive to the appetite-stimulating effects of ghrelin and inhibition of circulating ghrelin may be a useful therapeutic target in the treatment of obesity.