Progesterone receptor (PR) expression is highly dependent on estradiol in the medial preoptic nucleus (MPN) and the ventromedial nucleus (VMN) of the adult rat brain. During development, males express high levels of PR in the MPN, whereas females have virtually no PR, a sex difference resulting entirely from differential exposure to estradiol. Because PR is also estradiol dependent in the adult VMN, the present study examined the regulation of PR immunoreactivity (PRir) in the developing VMN. Surprisingly, PRir was present at high levels in the VMN of both neonatal males and females. In the neonatal VMN, PR expression was dependent on gonadal hormones in males but not females. When females were ovariectomized and exposed to estradiol at various ages from neonatal to adulthood, estradiol reliably induced PRir in the MPN at postnatal d 7 but failed to induce PRir in the VMN of the same animals. Only later in development, around postnatal d 14, did estradiol increase PRir in the female VMN. There appears to be a developmental switch in the VMN when PR expression changes from estradiol independent to estradiol dependent. Furthermore, this switch is anatomically specific and does not exist in the MPN. The present results indicate that the regulation of PR expression by estradiol is dependent on age, sex, and brain region, suggesting that PR may play a critical but specific role in the normal development of these reproductively important brain areas. In addition, the neonatal female VMN may provide a unique model in which to examine the mechanisms underlying the specificity of steroid-induced gene expression.