Steroid hormones influence the development of numerous brain regions, including some that are not classically considered steroid-sensitive. For example, nuclear receptors for both androgen and estrogen have been detected in neonatal cortical cells. High levels of progestin binding and progestin receptor (PR) mRNA have also been reported in early perinatal isocortex. PR expression coincides with high levels of de novo progesterone produced within the cortex, suggesting that PR and its ligand influence the important developmental cortical processes occurring shortly after birth. In order to better understand the role PR plays in cortical development, we used the cellular-level resolution of immunohistochemistry and in situ hybridization (ISH) to characterize changes in perinatal PR expression within specific cortical lamina. PR immunoreactivity (PR-ir) was examined at embryonic days (E) 18, 20, 21, 22, and postnatal days (P) 1, 3, 6, 9, 13, and 27. We find that PR-ir is transiently expressed in specific lamina of frontal, parietal, temporal, and occipital cortex. PR-ir was observed in subplate cells on E18, in increasingly superficial lamina (primarily lamina V, then II/III) during early postnatal development, and was absent by P27. Double-labeling immunohistochemistry indicated that PR-ir colocalizes with the neuronal marker, microtubule associated protein-2, but not with the glial marker, nestin, nor with gamma-aminobutyric acid. These results suggest that specific subpopulations of cortical neurons may be transiently sensitive to progesterone, and that progesterone and its receptor may play a critical role in the fundamental mechanisms underlying normal cortical development.