Endoglin (CD105) is a cell surface antigen widely expressed on vascular endothelium, syncytiotrophoblast, some tissue macrophages, certain culture cells (including early leukemic B-lineage) and some endothelial cell lines. Though its relation to the transforming growth factor-beta (TGF-beta) receptor system is well documented, its function and detailed pattern of expression still remain to be clarified. We examined the differential tissue distribution of endoglin in human lymphoid organs and placenta with several anti-CD 105 monoclonal antibodies (mAbs) using an indirect immunoperoxidase technique, and performed semi-quantitative measurements using an image-analyzing system for comparison. Arterial, venous and capillary endothelia in these organs were reactive with anti-CD 105 mAbs at varying intensities. Interestingly, a distinctly stronger staining pattern was observed in the high endothelial venules (HEVs) which may indicate a special role for endoglin in lymphocyte trafficking. Syncytiotrophoblast expressed endoglin strongly on their apical cell membrane. Extravillous trophoblasts at certain locations selectively expressed endoglin on their cell membranes, suggesting a special role for this surface antigen during trophoblast differentiation.