The aim of this study was to determine the effects of a clinically relevant single course of prenatal betamethasone in the rat on growth parameters with particular reference to brain cell proliferation and apoptosis. We report that administration of 170 µg/kg betamethasone twice within four hours to E20 pregnant rats conveys moderate somatic growth retardation. Further, using a measure of brain cell proliferation independent of blood brain barrier (BBB) permeability, we demonstrate for the first time that betamethasone is chronically anti-proliferative to brain cells without inducing caspase-3 mediated apoptosis. More importantly we show that there is a significant and sexually divergent rebound of neural proliferation which occurs earlier in males than in females and continues until at least 21 days of postnatal life. BBB permeability to 3H thymidine was significantly increased by steroid treatment re-iterating the fact that tracer studies not correcting for BBB permeability, like bromodeoxyuridine (BrdU), may be questionable in this type of study. Further, prenatal steroid treatment did not alter postnatal corticosterone levels. In summary we show that prenatal betamethasone conveys significant and long lasting side effects and that its clinical application in preterm labor needs more careful consideration as compared to the relative ease with which it is prescribed today.