The rate of synthesis of myofibrillar proteins is slower in muscle of healthy subjects over 60 yr old than it is in young adults. Previous research suggests that reduced activity of the GH/insulin-like growth factor-I system could be a determinant of this slowing of protein synthesis. To test the hypothesis that GH could rejuvenate the rate of myofibrillar protein synthesis, we studied healthy subjects over 60 yr old, after a single injection (0.03 mg/kg.sc) of recombinant human GH (n = 6 males/2 females) or placebo (n = 6 males/2 females), or after 3 months of either GH (0.03 mg/kg, sc, 3 x /week, n = 5 males) or placebo (n = 5 males) treatment. Myofibrillar protein synthesis and whole-body protein metabolism were evaluated with the tracer L-[1-13C]leucine. GH reduced whole-body leucine oxidation by 36% (P < 0.01) in the single injection study. There was no effect of GH on whole-body protein breakdown or synthesis, or on myofibrillar protein synthesis in the quadriceps, either acutely or after 3 months of treatment. GH treatment for 3 months increased lean body mass (3.3 +/- 0.7 kg, P < 0.01, as evaluated by 40K counting), muscle mass (3.3 +/- 1.1 kg, P < 0.02, as evaluated by urinary creatinine excretion), and thigh strength (14 +/- 5%, P < 0.05, as evaluated by isokinetic dynamometry). We conclude that GH can increase muscle mass and strength in healthy men over 60 yr old, but does not restore a youthful rate of myofibrillar protein synthesis.