A regimen of twice daily metyrapone injections (100 mg/kg), resulted in pharmacological adrenalectomy of pregnant rats and fetuses in utero, i.e. depression of plasma corticosterone and elevation of plasma adrenocorticotropic hormone (ACTH). Toxicity was minimal on days 14-17 of pregnancy, and increased with higher maternal weight and pregnancy progression. Corticotropin releasing hormone (CRH) messenger RNA abundance in the pregnant adults increased significantly within 48 h of metyrapone initiation. No change in CRH gene expression in the paraventricular nucleus of fetuses (days 17-18) was seen, even after 72 h of the regimen. This is compatible with the independence of CRH gene expression of glucocorticoid feedback in the fetal rat.