Aging is associated with reduced activities of the growth hormone (GH), insulin-like growth factor I (IGF-I), and sex steroid axes, and with decreased lean body mass and protein synthesis. Using a randomized, double-blinded, placebo-controlled design, we studied the effects of 6 months of administration of GH alone, sex hormone alone (hormone replacement therapy in women, testosterone enanthate [T] in men), or GH plus sex hormone on protein turnover in healthy men (n=60) and women (n=43), aged 65 to 88 years (mean, 71+/-4.4 years). Growth hormone administration significantly increased IGF-I levels in both sexes, more markedly in men. Sex steroid administration increased the levels of estrogen and testosterone in women and men, respectively (P=.05). Protein turnover was measured before and after the 26-week treatment period by means of a primed, constant l-[1-(13)C]leucine infusion. In men, GH plus T administration increased leucine flux from 80.2+/-2.8 to 93.6+/-4.2 micromol.h-1.kg-1 (P=.02). Leucine oxidation did not change significantly after hormone treatment in either sex. Growth hormone treatment led to nonsignificant upward trends in nonoxidative leucine disposal in men (9.1+/-5.2 mol.h-1.kg-1) and women (7.6+/-7.1 mol.h-1.kg-1). Among all groups combined, changes in nonoxidative leucine disposal were directly related to those of serum IGF-I level (r=0.248, P<.02). Whole-body protein turnover increased in GH plus T-treated men (0.6+/-0.2 g protein.kg-1.d-1; P<.01). These data suggest that low-dose GH administration increases protein synthesis in healthy aged women and men, and that the coadministration of testosterone plus GH enhances this effect in elderly men.