The results of more than four decades of research on different mammalian species have established that the brain, like the rest of the reproductive system, is esentially basically female. For the male to develop structural and functional characteristics typical of his species, his brain must be exposed to testicular hormones during a critical period, or critical periods, of development. As mammals, human beings are most likely subject to this process of the hormone-dependent sexual differentiation of the brain, but proving it will be difficult. Common sense ethics preclude experimental procedures such as castration of neonatal infants or exposing the female fetus to testosterone perinatally. Thus, scientists are restricted to the retrospective study of "Experiments of Nature." The results of such studies support to a degree a meaningful role of hormones in the development of the human brain. The concept of the sexual differentiation of brain structure and function has a potentially profound influence on clinical decisions with respect to sex assignment and clinical management of infants with ambiguous or poorly developed external genitalia. Because of the importance of a baby's sex in our culture, parents of such infants must be given consideration, but so should the infant whose hormonal environment prenatally may well have produced permanent changes in the structure and functional potential of his/her brain.