We investigated the effects of 6 mo of near-physiological testosterone administration to older men on skeletal muscle function and muscle protein metabolism. Twelve older men (> or =60 yr) with serum total testosterone concentrations <17 nmol/l (480 ng/dl) were randomly assigned in double-blind manner to receive either placebo (n = 5) or testosterone enanthate (TE; n = 7) injections. Weekly intramuscular injections were given for the 1st mo to establish increased blood testosterone concentrations at 1 mo and then changed to biweekly injections until the 6-mo time point. TE doses were adjusted to maintain nadir serum testosterone concentrations between 17 and 28 nmol/l. Lean body mass (LBM), muscle volume, prostate size, and urinary flow were measured at baseline and at 6 mo. Protein expression of androgen receptor (AR) and insulin-like growth factor I, along with muscle strength and muscle protein metabolism, were measured at baseline and at 1 and 6 mo of treatment. Hematological parameters were followed monthly throughout the study. Older men receiving testosterone increased total and leg LBM, muscle volume, and leg and arm muscle strength after 6 mo. LBM accretion resulted from an increase in muscle protein net balance, due to a decrease in muscle protein breakdown. TE treatment increased expression of AR protein at 1 mo, but expression returned to pre-TE treatment levels by 6 mo. IGF-I protein expression increased at 1 mo and remained increased throughout TE administration. We conclude that physiological and near-physiological increases of testosterone in older men will increase muscle protein anabolism and muscle strength.