BACKGROUND: Treatment with high doses (2-6 mg day(-1)) of human growth hormone (hGH) in patients with human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) has been shown to increase concentrations of total insulin-like growth-factor-I (IGF-I) more than twofold greater than the normal upper range and is accompanied by adverse effects such as joint pain and glucose intolerance. MATERIALS AND METHODS: We performed a 16-week open-labelled prospective pilot study in six male HALS patients using a s.c. low-dose hGH, 0.7 mg day(-1), aiming to examine the impact on total and free IGF-I and fat distribution. Glucose metabolism was examined by oral glucose tolerance tests and hyperinsulinaemic euglycaemic clamps. RESULTS: Total IGF-I increased twofold (P < 0.01) and free IGF-I increased 2.5-fold (P < 0.01) to the level of the normal upper range. HDL-cholesterol increased (P = 0.01). Patients reported improvements of lipodystrophy, which was supported by a decreased waist-to-thigh ratio (P = 0.01), and waist-to-hip ratio (P = 0.06). Ratio of peripheral to trunk soft tissue mass increased (P = 0.01, measured by dual-energy X-ray absorptiometry scans) and a trend towards reduction in percentage of trunk fat was suggested (P = 0.12). Total fat mass, exercise capacity, glucose tolerance, glucose disposal rate and immune status, respectively, did not change (all P > 0.5). The patients did not complain of arthralgia or other known GH-related side-effects. CONCLUSIONS: Sixteen weeks' treatment of lipodystrophic HIV-infected patients with hGH, 0.7 mg day(-1), increased total and free IGF-I twofold and appeared safe and tolerable. The potential of low-dose hGH in the treatment of HIV-lipodystrophy awaits examination by placebo-controlled, randomized trials.