Myostatin inhibits skeletal muscle development. Therefore, we sought to determine whether larger body and muscle mass in male mice was associated with lower mRNA and protein expression of myostatin compared with females. Ten male and ten female mice of the C57 strain were killed at 16-18 wk of age, and their biceps femoris, gastrocnemius, and quadriceps femoris muscles were collected. Body and muscle masses were 40% heavier (P < 0.001) in males than in females. Northern analysis showed no difference in mRNA between males and females. In contrast, Western analysis showed that processed myostatin (26 kDa) was 40-60% lower (P < 0.001) in males compared with females. These data show first that decreased processed myostatin is a posttranscriptional and posttranslational event and, second, that decreased abundance of processed myostatin is associated with increased body mass and skeletal muscle mass in male compared with female mice.