Recent reports of disruptive mutations of the genes for the estrogen receptor or for cytochrome P-450 aromatase¹–⁶ have shed new light on the role of estrogen. In females the lack of estrogen due to aromatase deficiency leads to pseudohermaphroditism and progressive virilization at puberty, whereas in males pubertal development is normal. In members of both sexes epiphyseal closure is delayed, resulting in a eunuchoid habitus, and osteopenia is present.⁶ These findings suggest a crucial role of estrogen in skeletal maturation.¹–⁶ We describe the responses to androgen and estrogen in a man with a novel, homozygous inactivating mutation of . . .