The question of the transport of proteins across the placenta is controversial. Either a chorio-allantoic or a yolk sac transfer is possible. After injecting electron dense markers one may trace the molecules from the maternal towards the foetal circulation at an ultrastructural level. More refined cytochemical methods employing enzyme markers have unravelled many problems related to fluid flow in various organs. The authors used horseradish peroxidase (HRP), a protein with a molecular weight of 40,000 and diameter of 40A to delineate the placental pathways in full term, pregnant, albino mice. The rodents were lightly anaesthetized with ether and injected intravenously on the 20th day of gestation with Sigma type II HRP in doses of 0.1 mg./g. body weight dissolved in 0.5 ml. of N saline. Placental and yolk sac biopsies were taken at ½, 2, 5, 10, 30,45 and 60 min. intervals. Control animals received normal saline only. The tissues, after glutaraldehyde fixation (6.25%), were washed overnight in 0.1M cacodylate buffer (pH 7.4) and sections were obtained by chopping them in agar on a Sorvall tissue chopper at a thickness of 40μ. The sections were left for 5-10 min. in a substrate composed of a saturated solution of 3-3' diaminobenzidine in tris-HCl buffer containing 0.01 % hydrogen peroxide; they were then postfixed in 1 % osmium tetroxide for 90 min. Substrate controls included omission of hydrogen peroxide or the diaminobenzidine. The sections were then prepared conventionally for electron microscopic examination by embedding in araldite. Although HRP was identified in the chorio-allantoic placenta, no direct and continuous passage was observed from the maternal to the foetal circulation in this structure. On the other hand the enzyme penetrated the parietal yolk sac by ½ min. so that its lumen soon contained a massive accumulation. Thereafter the HRP was traced in vesicles and vacuoles through the columnar endodermal cells of the visceral yolk sac, finally crossing the basement membrane to enter the mesothelial cells lining the exocoelom or the endothelial cells of vitelline capillaries. These results indicated that the passage of proteins of the size of HRP occurred at term from the maternal to foetal circulation across the yolk sac rather than the chorioallantoic placenta. Absorption could take place either through the foetal gut after the entry of the protein into the exocoelom or by a more direct access through the vitelline capillaries.