Obese individuals are in a reduced GH/IGF-I state that may be maladaptive. Fifty-nine obese men and premenopausal menstruating women (body mass index, 36.9 +/- 5.0 kg/m(2)) were randomized to a double-blind, placebo-controlled trial of low dose recombinant human GH (rhGH). During the 6-month intervention, subjects self-administered daily rhGH or equivalent volume of placebo at 200 micro g (1.9 +/- 0.3 microg/kg for men, 2.0 +/- 0.3 microg/kg for women); after 1 month, the dose was increased to 400 microg (3.8 +/- 0.5 microg/kg) in men and 600 microg (6.0 +/- 0.8 microg/kg) in women. rhGH was then discontinued, and subjects were followed up after 3 months. Forty completed the intervention, and 39 completed the follow-up. Drop-out rates between rhGH vs. placebo groups were not different (chi(2) = 1.45; P = 0.228). One subject discontinued the drug due to an rhGH-related side effect. Body weight (BW) decreased with rhGH from 100.4 +/- 13.2 to 98.0 +/- 15.6 kg at 6 months (P = 0.04) and was sustained at 98.1 +/- 16.6 kg at 9 months (P = 0.02). BW loss was entirely due to loss of body fat (BF). Intention to treat analyses demonstrated changes from baseline between rhGH and placebo in BW (-2.16 +/- 4.48 vs. -0.04 +/- 2.67 kg; P = 0.03) and BF (-2.89 +/- 3.76 vs. -0.68 +/- 2.37 kg; P = 0.01). rhGH increased IGF-I from -0.72 to +0.10 SD (P = 0.0001). rhGH increased high-density lipoprotein cholesterol 19% from 1.11 +/- 0.34 to 1.32 +/- 0.28 mmol/liter (P < 0.001). Neither group had changes in fasting glucose, insulin sensitivity, or resting energy expenditure. In conclusion, in obesity, rhGH normalized IGF-I levels, induced loss of BW from BF, and improved lipid profile without untoward effects on insulin sensitivity.