Ontogeny of fetal plasma proteins was investigated. By 4.5 weeks' gestation, the yolk sac synthesizes prealbumin, albumin, alpha 1-antitrypsin, alpha fetoprotein (AFP), and transferrin. Synthesis of immunoglobulin M (IgM), IgG, IgE, and IgD begins around 10-11 weeks' gestation. By 17-18 weeks' gestation, lymphoid cells are distinguishable in the spleen, and the spleen then becomes the major single organ for IgM and IgG production. It rises rapidly to a maximum of 300 mg% at 10-13 weeks which is due entirely to endogenous synthesis. Serum AFP then falls exponentially with a 1/2 life of about 32 days. After 32 weeks' gestation, the AFP level falls rapidly, indicating a sharp reduction in total AFP production. Synthesis of AFP is still evident at term in at least some normal fetuses. Cortisone acetate administered to pregnant rats just prior to parturition resulted in fetal suppression of AFP synthesis. Evidence indicates that cortisone acts only indirectly on the synthesizing pathway.