The aim of this study was to investigate the occurrence of polymorphisms of the beta-adrenergic receptor gene in short children and to evaluate the possible influence of the polymorphisms on changes in height and obesity index in response to GH treatment. Of the 75 children enrolled in the study, 40 completed at least 5 years of GH treatment. The genotype distribution of the beta2 and 3-adrenergic receptor polymorphisms in the study population did not differ significantly from those reported in non-obese subjects. There were no significant differences in the SD score for height at any given time-point between the group with and without the Trp64Arg mutation of the beta3-adrenergic receptor gene. In relation to the Glyl6Arg polymorphism of the beta2-adrenergic receptor gene, the mean SD score for height increased significantly during GH treatment in children with Argl6Arg and Glyl6Arg. In those with Glyl6Gly, the score did not show any significant increase during all 5 years of GH treatment. In both the groups with and without the Trp64Arg mutation, the changes in obesity index did not reach statistical significance at any time-point. Only children with Glyl6Gly had a significantly higher baseline mean obesity index than those with Glyl6Arg. The index also decreased markedly from 21.9% to 5.8% in these children during the first 4 years of GH treatment. Thus, when the impact of the polymorphisms of these two receptor genes was studied simultaneously, it appeared that only the beta2-adrenergic receptor polymorphism had an important role to play in modulating the regulation of growth rate and energy expenditure in short children.