Growth hormone (GH) induces lipolysis and an increase of free fatty acids (FFA), and FFA inhibit the GH response to arginine and to GH-releasing hormone (GHRH). The aim of this study was to evaluate the effect of the pharmacologic blockade of lipolysis on the GH response to GHRH. Eleven normal men underwent a saline infusion starting at 09:00 h, after administration of placebo or 500 mg acipimox, an antilipolytic agent; at 13:00 h (0 min) they received GHRH, 50 micrograms iv The GH response to GHRH (0 to 120 min) was significantly higher in subjects pretreated with acipimox than in subjects pretreated with placebo. In subjects receiving placebo, but not in those receiving acipimox, a progressive increase of plasma FFA levels took place, and the GH response to GHRH was inversely related to the plasma FFA levels at 0 min. These data indicate that FFA play an important role in the control of GH release, and that acipimox prevents the FFA rise induced by GH.