Adult male and female humans have clear differences in muscle mass and there is mounting evidence that substrate metabolism differs between genders. These facts suggest that there are gender differences in protein metabolism between males and females. Studies utilizing stable isotopically labeled amino acids show little indication that whole body protein synthesis or breakdown is different between genders. There is evidence that leucine oxidation may be different, both at rest and during exercise, but this evidence is not unequivocal and more, properly controlled studies need to be undertaken to clarify this controversy. Muscle hypertrophy results from positive net muscle protein balance, thus, adult males must have greater net muscle protein synthesis than females, at least at some point in development. Although there is a paucity of data, no gender differences in the basal level net muscle protein balance have been found. It is possible that there are small differences that cannot be distinguished with current methods due to small sample sizes and the sensitivity of the methods. It is more likely, however, that sex hormones contribute to the clear differences in musculature by influencing muscle protein metabolism, especially during puberty. Testosterone increases muscle protein synthesis and net muscle protein balance, resulting in increased muscle mass. Males and females have similar amounts of testosterone until puberty, then testosterone levels increase much more dramatically in males, as does muscle mass. Furthermore, although no evidence exists in humans, in-vitro and rat data suggest that ovarian hormones inhibit muscle protein synthesis. Whereas solid conclusions are difficult to make given the paucity of studies focusing on gender differences in human protein metabolism, it seems that the sex hormones may play an important role. Certainly, more studies need to be conducted to ascertain what gender differences in whole body and muscle protein metabolism exist and how these differences result in different phylogenetic characteristics.