In order to investigate whether ACTH can cross the placenta of the rat at term, porcine 125I-ACTH was injected into mothers or fetuses. ACTHwas then extracted from maternal and fetal plasma, using QUSO G-32, 2.5, 5, 10, 15 and 20 min after the injection of labelled ACTH. Plasma samples were also chromatographed on Sephadex G-50, fine, columns, 5 and 20 min after the administration of ACTH. When 125I-ACTH was injected into the mothers, the two methods used were unable to detect any radioactivity associated with intact ACTH in the fetal plasma. The same was observed in the maternal plasma when labelled hormone was administered to the fetuses. These observations provide direct experimental proof of the absence of transplacental passage in the rat of 125I-ACTH from the mother to the fetus as well as from the fetus to the mother.