The ratio between the second digit (2D) and fourth digit (4D) length differs between human males and females. 2D is generally shorter than 4D in males (2D:4D < 1), whereas 2D is typically the same or longer than 4D in females (2D:4D ≥ 1). Zheng and Cohn report (Proc. Natl. Acad. Sci. USA, published online 6 September 2011; doi:10.1073/pnas.1108312108) that similar 2D:4D sexual dimorphism occurs in mice and that it is regulated by the balance of androgen to estrogen signaling in utero. The difference in androgen receptor (AR) activity between 2D and 4D was greater in males, whereas the difference in estrogen receptor (ER-α) activity was greater in females, suggesting that the relative difference in androgen versus estrogen activity controls this trait. Males lacking AR showed increased 2D:4D ratios, whereas males lacking ER-α had decreased 2D:4D ratios. AR thus seems to be required for the masculine (low) 2D:4D ratio, whereas ER-α is needed for the feminine (high) 2D:4D ratio. Inhibiting AR pharmacologically caused a 40% reduction in chondrocyte proliferation in 4D but only a 20% reduction in 2D, accounting for decreased growth of 4D and the subsequent increased 2D:4D ratio. In contrast, inactivating ER-α increases growth of 4D, leading to a lower 2D:4D ratio. The authors conclude that the 2D:4D ratio is controlled by uterine hormones, implying that the 2D:4D ratio may be a valid index of uterine environment.