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To investigate the effect of growth hormone (GH) treatment on skeletal muscle protein catabolism in patients with multiple organ failure in the intensive care unit (ICU).Skeletal muscle depletion affects the incidence of complications and the length of hospital stay. A protein-sparing effect of GH treatment in skeletal muscle of long-term ICU patients was hypothesized.Twenty critically ill ICU patients were randomized to treatment with GH (0.3 U/kg/day) or as controls. Percutaneous muscle biopsy samples were taken before and after a 5-day treatment period starting on day 3 to 42 of the patient’s ICU stay. Protein content, protein synthesis, water, nucleic acids, and free amino acids in muscle were analyzed.The protein content decreased by 8% ± 11% in the control patients, with no significant change in the GH group. The fractional synthesis rate of muscle proteins increased in the GH group by 33% ± 48%, and muscle free glutamine increased by 207% ± 327% in the GH group. Total intramuscular water increased by 12% ± 14% in the control group as a result of an increase in extracellular water of 67% ± 86%; these increases were not seen in the GH group. In contrast, the intracellular water increased by 6% ± 8% in the GH group.Treatment with GH for 5 days in patients with multiple organ failure stimulated muscle protein synthesis, increased muscle free glutamine, and increased intracellular muscle water.