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Development of the male urogenital tract in mammals is mediated by testicular androgens. It has been tacitly assumed that testosterone acts through its intracellular metabolite dihydrotestosterone (DHT) to mediate this process, but levels of these androgens are not sexually dimorphic in plasma at the time of prostate development. Here we show that the 3␣-reduced derivative of DHT, 5␣-androstane-3␣,17␤-diol (5␣-adiol), is formed in testes of tammar wallaby pouch young and is higher in male than in female plasma in this species during early sexual differentiation. Administration of 5␣-adiol caused formation of prostatic buds in female wallaby pouch young, and in tissue minces of urogenital sinus and urogenital tubercle radioactive 5␣-adiol was converted to DHT, suggesting that circulating 5␣-adiol acts through DHT in target tissues. We conclude that circulating 5␣-adiol is a key hormone in male development. I n all mammalian species testicular androgens control three aspects of male phenotypic development-conversion of the wolffian ducts into the epididymis, vas deferens, and seminal vesicles; formation of the male urethra and prostate; and formation of the phallus (1). Studies in animals and humans with mutations in the genes that encode the androgen receptor or steroid 5␣-reductase 2 indicate that testosterone virilizes the wolffian ducts and that 5␣-reduced androgens are essential for formation of the prostate and phallus (1). Because virilization occurs during early fetal development in eutherian mammals, it has not been possible to measure androgens in the circulation when virilization begins.Marsupial mammals offer an advantage for studying male phenotypic development, which takes place after birth when the young are easily accessible in the pouch and over a longer period than in the eutherian, so that it is possible to study the various aspects of phenotypic development individually (2). Virilization of the urogenital tract in the male marsupial pouch young is similar to that in eutherian fetuses, except that formation of the scrotum in marsupials is androgen-independent (2-6). This process has been examined in detail in one marsupial species, the tammar wallaby, Macropus eugenii, in which formation of the prostate begins in the urogenital sinus at around day 20 postpartum (5), whereas virilization of the penis commences around day 100 (6). Testosterone concentrations in the testes increase before prostate formation begins (7), and prostate development can be prevented by administration of the steroid 5␣-reductase inhibitor finasteride (8), which blocks the formation of dihydrotestosterone (DHT), or of the androgen receptor inhibitor flutamide (9), which prevents the actions of both testosterone and DHT. Administration of large amounts of testosterone (5) or transplantation of testes to female pouch young (10) causes prostate development, whereas castration of 10-day-old male pouch young prevents formation of the prostate and penis (10).Despite the wealth of evidence for a crucial role of 5␣-reduced androge...