Growth hormone therapy is often associated with adverse side effects including impaired insulin sensitivity. Furthermore, GH treatment of children with idiopathic short stature does not lead to an optimised final adult height. It has been demonstrated that FFA reduction by pharmacological antilipolysis can stimulate GH secretion in normal subjects and in those with GH-deficiency. To date, no investigation has been undertaken to establish efficacy of combination treatment with GH and FFA regulators on linear body growth. Using maternal undernutrition in the rat to induce growth restricted offspring, we investigated the hypothesis that combination treatment with GH and FFA regulators can enhance linear body growth above that of GH alone. At day 28, male offspring of normally nourished mothers (controls) and offspring born of low birth weight (small for gestational age, SGA) were treated with saline, GH, or GH in combination with acipimox (GHA) or fenofibrate (GHF) for 40 days. GHA treatment significantly enhanced linear body growth in control and SGA animals above that of GH as quantified by tibial length and total body length. Treatment with GH significantly increased plasma insulin and plasma volumes in control and SGA animals but were not different between saline and GHA treated animals. GH-induced lipolysis was blocked by GHA treatment in control and SGA animals concomitant with a reduction in plasma FFA and insulin concentrations. This is the first study to show that GHA combination therapy can significantly enhance the efficacy of GH in linear growth promotion and ameliorate unwanted metabolic side effects.