Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor, has been reported to induce a GH-releasing, orexigenic effect on weight gain, and adipogenic actions. It is, therefore, thought that ghrelin links the regulatory systems for growth and energy balance.We examined 25 obese children undergoing a 3-month inpatient weight reduction program for obese children based on a combination of diet and exercise therapy and evaluated the change in the serum ghrelin levels.The subjects consisted of 25 children with moderate to severe simple obesity [17 boys, 8 girls ; mean age 9.9±1.3 years, percent overweight (% overweight) 52.1±13.6%]. Height, weight, percent body fat (% BF), fat mass, fat-free mass (FFM), and serum ghrelin were measured before and after weight reduction.After therapy, body weight, % BF and fat mass had all significantly decreased (p<0.001), while height and FFM had both significantly increased (p<0.001 ; p<0.05, respectively). There were no correlations between pre-therapy serum ghrelin and any of the following: initial height, weight, % overweight, % BF, fat mass, or FFM. However, after therapy, serum ghrelin levels were negatively correlated with body weight (r_s=-0.544, p<0.01). Serum ghrelin levels increased significantly from pre- to post-therapy (113.9±30.7 to 129.6±42.9 fmol/ml, p<0.05). The rate of changes in ghrelin levels was negatively correlated with the rate of change in the % overweight (r_s=-0.412, p<0.05).These findings suggest that long-term weight reduction based on a combination of diet and exercise therapy lessens the severity of obesity and increases serum ghrelin levels in obese children.