Objective: HIV lipodystrophy is a common complication of highly active anti-retroviral therapy, characterized by both metabolic and morphological features. The most feared morphological feature is body fat redistribution leading to HIV lipodystrophy. GH is known to induce reduction of visceral obesity and body fat redistribution in adults. Design: A crossover, double-blind protocol of GH treatment (6 months of recombinant human GH (rhGH) at 0.2 IU/kg per week) vs placebo (6 months of placebo with a 2 month wash-out between periods) was performed. Subjects and setting: Thirty HIV-infected patients with lipodystrophy were recruited in the Outpatient Clinic of the Division of Infectious Diseases of San Raffaele Scientific Institute in Milan, Italy. Main outcome and results: Our data demonstrate an effect of low-dose rhGH administration in reducing trunk adiposity in HIV patients with lipodystrophy (Δ from basal: −394 ± 814 g, P = 0.048 with respect to placebo. Data are given as mean ± standard deviation). A trend to an increase of arm depots was also shown (Δ from basal: +43 ± 384 g, P = NS with respect to placebo). Interestingly, no detrimental metabolic effects on glucose tolerance and lipid levels were found following the administration of 0.2 IU/kg per week of rhGH for 6 months. Conclusions: Low-dose GH administration is an effective treatment in reducing trunk obesity in HIV-infected patients with lipodystrophy.