A 91 kDa protein, sharing antigenicity with a pregnancy-associated antigen, was isolated from the ascitic fluid of a patient suffered from the gynaecological malignant neoplasms. It was revealed in the human placenta by immunocytochemical techniques, and found to be localized in the stroma, including a fibrous network, fibroblasts and the Hofbauer cells of the terminal and stem villi in the first trimester. Immunoreactive staining was also found in macrophage-like cells, presumable the precursor of the Hofbauer cell, in the stem villi of placenta. It is assumed that macrophage-like cells containing the protein would be originated from the extraembryonic mesoderm or blood vessels, and then migrated to the stroma of terminal villi. During the second trimester, the protein was observed in numerous vesicles among the syncytial trophoblasts. The density of these immunoreactive vesicles and the cytoplasm of Hofbauer cells was rapidly increased with gestational stages, whereas it was gradually reduced towards the late-second trimester. The highest labellings occurred at around 17 weeks or later. On the other hand, at term, the protein was mainly observed in numerous villous blood vessels including endothelial cells. In the light of these results, a hypothesis concerning mechanisms of transplacental permeability of the protein by the placental barrier is discussed further.