Chronic administration of exogenous GH to GH-deficient children is associated with a redistribution of adipose tissue from an abdominal (android) to a more peripheral (gynoid) distribution. We studied abdominal and gluteal sc adipose tissue from seven GH-deficient children 1) before beginning and 2) after 3 months of therapy with exogenous GH (0.1 mg/kg, sc, three times per week). In abdominal and gluteal adipocytes, we measured lipid content and rates of in vitro lipolysis and lipogenesis in response to insulin and various adrenoreceptor agonists. These results were correlated with measures of statural growth and adipose tissue distribution in each subject. We found that GH therapy was associated with a significant reduction in abdominal adipocyte size (0.68 +/- 0.09 micrograms lipid/cell before therapy vs. 0.49 +/- 0.07 after therapy; P less than 0.05), a significant reduction in overall basal rates of lipogenesis (0.43 +/- 0.06 mumol [14C]acylglyceride synthesized/10(6) cells.2 h before therapy vs. 0.27 +/- 0.09 after therapy), and with variable desensitization of abdominal sc adipose tissue to the antilipolytic effect of insulin. The extent of this decrease in insulin action was significantly correlated with changes in abdominal adipocyte lipid content (r = 0.77; P less than 0.05), and with the changes in the anatomical distribution of fat during the study period (r = 0.97; P less than 0.001), as measured by the relative lipid content per adipocyte at each site. We conclude that the site-specific changes in adipose distribution during GH administration are due in part to anatomical site-specific GH-mediated changes in insulin responsiveness of adipose tissue and that exogenous GH therapy is associated with a decrease in de novo triglyceride synthesis in GH-deficient children.