Androstenedione is the immediate precursor of testosterone. Androstenedione intake has been speculated to increase plasma testosterone levels and muscle anabolism. Thus, androstenedione supplements have become widely popular in the sport community to improve performance. This study was designed to determine whether 5 days of oral androstenedione (100 mg/day) supplementation increases skeletal muscle anabolism. Six healthy young men were studied before the treatment period and after 5 days of oral androstenedione supplementation. Muscle protein turnover parameters were compared to those of a control group studied twice as well and receiving no treatment. We measured muscle protein kinetics using a three-compartment model involving infusion of L-[ring-2H5]phenylalanine, blood sampling from femoral artery and vein, and muscle biopsies. Plasma testosterone, androstenedione, LH, and estradiol concentrations were determined by RIA. After ingestion of oral androstenedione, plasma testosterone and LH concentrations did not change from basal, whereas plasma androstenedione and estradiol concentrations were significantly increased (P<0.05). Compared to a control group, androstenedione did not affect muscle protein synthesis and breakdown, or phenylalanine net balance across the leg. We conclude that oral androstenedione does not increase plasma testosterone concentrations and has no anabolic effect on muscle protein metabolism in young eugonadal men.