The purpose of this study was to evaluate growth hormone (GH) secretion and clarify the factors influencing GH secretion in obesity. Nine obese subjects and eight controls were recruited. We compared the GH response to L-dopa with or without pyridostigmine pretreatment in obese and control subjects. Plasma glucose, insulin, insulin-like growth factor I (IGF-I) and free fatty acid (FFA) were also measured. Growth hormone responses and GH area under the response curve (AUC) to L-dopa were significantly lower in obese subjects than those in controls. Pyridostigmine significantly enhanced the GH response to L-dopa in both obese and control subjects. However, enhanced GH responses in obese subjects were attenuated biologically and lower than those in controls with L-dopa only. Plasma levels of insulin insulin and FFA were significantly higher in obese subjects than those in controls. Body mass index had a positive correlation with the levels of insulin and FFA. However, GH AUC had an inverse correlation with insulin and FFA in obese subjects and controls. Stepwise multiple regression analysis showed a highly significant effect of FFA on GH AUC, but no independent influence of other factors on GH AUC. The reduced GH secretion found in this study suggests an increase in somatostatinergic tone and a diminished release of GHRH from the hypothalamus in obesity. However, other factors including hyperinsulinemia and increased plasma FFA may play an important additional role in the secretory dysfunction of GH in obesity.