We hypothesized that a high circulating FFA concentration is involved in the pathogenesis of hyposomatotropism associated with obesity. To evaluate this hypothesis, ten healthy premenopausal women (BMI 33.8 ±1.0 kg/m²) were studied in the follicular phase of their menstrual cycle at two occasions with a time interval of at least 8 weeks, where body weight remained stable. Subjects were randomly assigned to treatment with either Acipimox (an inhibitor of lipolysis, 250 mg orally four times daily) or placebo in a double blind cross-over design, starting one day prior to admission until the end of the bloodsampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of GH concentrations and GH secretion was estimated by deconvolution analysis. Identical methodology was used to study GH secretion in a historical control group of age-matched normal weight women. GH secretion, was clearly blunted in obese women (total daily release 66 ±10 vs lean controls: 201 ± 23 mU/L_Vd/24 h, P=0.005). Acipimox considerably enhanced total (113 ±50 vs 66 ±10 mU/L_Vd/24 h, P=0.02) and pulsatile GH secretion (109 ±49 vs 62 ±30 mU/L_Vd/24 h, P=0.02), but GH output remained lower compared to lean controls. Further analysis did not show any relationship between the effects of Acipimox on GH secretion and regional body fat distribution. In conclusion, Acipimox unleashes spontaneous GH secretion in obese women. It specifically enhances GH secretory burst mass. This might mean that lowering of systemic FFA concentrations by Acipimox modulates neuroendocrine mechanisms that orchestrate the activity of the somatotropic ensemble.