Human sex determination is a fascinating topic, particularly at the level of molecular genetics, as it represents an excellent paradigm for mammalian organ development. Recent progress has seen the addition of several new pieces to this developmental jigsaw puzzle. In mammals, the Y chromosome is male determining, and encodes a gene referred to as TDF (testis-determining factor), which induces the indifferent embryonic gonad to develop as a testis. Subsequent male sexual differentiation is largely a consequence of hormonal secretion from the testis. In the absence of the Y chromosome, the testis-determining pathway fails to be initiated, and the embryonic gonad develops as an ovary, resulting in female development. (Ford et al. [1959] Lancet i:711; Jacobs and Strong [1959] Nature, 183:302-303; Jost et al. [1973] Rec. Prog. Horm. Res., 29:1-41).