Sexual differentiation of female mammals has been viewed as an essentially passive process, i.e., what happens in the absence of androgen production by the fetal/neonatal testis during critical stages of development. However, the female spotted hyena (Crocuta crocuta) displays substantial plasma levels of androgens throughout life. The presence of these natural androgens is correlated with extreme "masculinization" of the external genitalia. Adult female hyenas are also heavier and more aggressive than males, while young females participate in vigorous social play as frequently (or more frequently) than males. If our current understanding of sexual differentiation is correct, the genital "masculinization" of the female hyena must have been caused by androgens circulating during fetal life. The presence of these natural androgens should also facilitate vigorous social play, enhance aggressive behavior and promote the large body size of female hyenas. In addition, both male and female neonatal hyenas engage in intense, intersibling fighting within minutes after birth. In nature, this commonly results in the death of one member of the twins that generally constitute a hyena litter, if both siblings are of the same sex. The central concern of our proposed research program is the role of endogenous androgens on sexual differentiation of morphology and behavior in the female spotted hyena. Specific aims include investigation of: (1) the novel possibility that mothers "masculinize" their female offspring through ovarian secretion of androstenedione, which is converted to testosterone by the placenta and passed to the developing fetus; (2) the role of fetal/neonatal androgens in promoting the intense neonatal aggression observed in male and female spotted hyenas; and (3) the effects of ovarian steroids on sexual and aggressive behaviors in adult female hyenas. Studies of sexual differentiation will involve: (a) determination of steroid levels in various fetal/maternal compartments during fetal development; (b) interference with actions of androgens during critical stages of fetal/neonatal life, using anti-androgens; and (c) elimination of potential sources of endogenous androgens. Morphological and behavioral consequences of these manipulations will be assessed throughout life. In terms of long range goals, we are using an "extreme" female mammal to reveal mechanisms of endogenous androgenic influence that might operate naturally, to less obvious extent, in all female mammals; as well as clarifying processes underlying certain human birth defects.