The interaction between testosterone and exogenous amino acids was studied in older men before and after 6 months of testosterone administration. Twelve healthy older male subjects were randomly assigned in double-blind fashion to receive either testosterone enanthate [T; n = 7; 68 +/- 3 (+/-SE) yr] or placebo (n = 5; 67 +/- 3 yr) for 6 months. Muscle protein kinetics were determined using stable isotope methodology, arterial-venous difference across leg muscle, and muscle biopsies. In addition, ubiquitin-proteasome activity was measured in muscle biopsies as an indicator of muscle protein breakdown. T improved fasting net protein balance, although it remained significantly negative. The improvement in net balance was due to a decrease in muscle protein breakdown, as protein synthesis was unchanged. Ubiquitin-proteasome activity was also decreased with T. Exogenous amino acids increased protein synthesis in both placebo and T groups, but to a lesser degree after 6 months of T treatment. These results indicate that prolonged T administration increases net protein balance in the fasted state, but no additive effect is demonstrated when combined with amino acid feedings. Taken together, however, these diverse stimulatory effects can increase lean body mass and muscle strength over time.