Muscle wasting in myotonic dystrophy may result from decreased muscle anabolic processes rather than from increased catabolism. Male patients with myotonic dystrophy often have low levels of circulating androgens, and androgen administration has been shown to increase their muscle mass. We have studied the effect of testosterone enanthate administration (3 mg/kg weekly for 3 months) on muscle and whole body protein synthesis in 6 male patients with myotonic dystrophy. Muscle protein synthesis was estimated from the rate of isotope incorporation into muscle protein obtained by quadriceps muscle biopsy during a primed continuous infusion of L-[1-13C]leucine. Testosterone administration resulted in a significant increase in muscle protein synthesis in all patients. Whole body protein synthesis did not increase, indicating that protein synthesis in other tissues may have declined. Muscle ribonucleic acid content rose significantly in response to testosterone administration, suggesting that testosterone initiated its effect by hormone receptor interaction with muscle nuclei.