Haem proteins of different molecular sizes were perfused into the foetal circulation of the guinea-pig placenta to study the permeability of the foetal endothelium. The smallest molecules tested, microperoxidase (ae 1.0 nm) and cytochrome C (ae 1.5 nm), readily penetrated the endothelium; tracer-reaction product was found in the subendothelial space of the capillaries. However, there was no uptake of these two tracers into the syncytiotrophoblast layer of the placenta. An intermediate-sized molecule, myoglobin (ae 1.7 nm) produced only a weak reaction product in the subendothelial space even when perfused at high concentration. The largest molecule tested, haemoglobin (ae 2.8 nm), did not penetrate the foetal endothelium at any of the concentrations employed. The foetal capillary endothelium thus provided a barrier to protein penetration from the foetal circulation, dependent on molecular size. There was evidence that the site of this barrier was located in the lateral intercellular spaces between the endothelial cells. The syncytiotrophoblast of this haemomonochorial placenta provided an almost absolute barrier to protein penetration from the foetal circulation. As other workers have described maternal-to-foetal transmission of proteins across this layer in the guinea-pig, a working hypothesis of the role of endothelium and syncytiotrophoblast in maternal/foetal protein exchange is discussed.