In rats, fetal testosterone directs sexual differentiation of the brain. However, fetuses are also exposed to maternal progesterone. Here we report that progestin receptor immunoreactivity in the medial preoptic nucleus (MPN) of fetal and neonatal rats is high in males but virtually absent in females. The MPN is one of the most sexually dimorphic structures in the rat brain and mediates several sexually differentiated behaviors. This suggests that progesterone may play a previously overlooked role in the development of sex differences in the brain and behavior. Henceforth, a novel function of the mother in the sexual differentiation of the CNS must be considered.