As a consequence of genetic sex determination, the indifferent gonadal blastema normally becomes either a testis or an ovary. This applies to mammals and to the majority of non-mammalian vertebrates. With the exception of placental mammals, however, partial or complete sex inversion can be induced in one sex by sexual steroid hormones of the opposite sex during a sensitive period of gonadogenesis. There is evidence that also during normal gonadogenesis in these species, in the XY/XX mechanism of sex determination testicular differentiation is induced by androgens, and in the ZZ/ZW mechanism, ovarian differentiation by oestrogens. In either case, the hormones may act via serological H-Y antigen as a morphogenetic factor. In contrast, in placental mammals including man, primary gonadal differentiation is independent of sexual steroid hormones, and factors directing differential gonadal development have not yet been conclusively identified. However, various mutations at the chromosome or gene level, resulting respectively in sex inversion or intersexuality, have provided clues as to some genes involved and their possible nature. In this context also, serological H-Y antigen is discussed as a possible factor acting on primordial gonadal cells and inducing differential growth or morphogenesis or both. The data available at present allow a tentative outline of the genetics of sex determination in placental mammals.