In addition to plasma the presence of subunit a of blood coagulation Factor XIII (FXIIl) has been verified in platelets and megakariocytes. Most recently, we demonstrated that human peripheral blood monocytes also contain FXIII subunit a. The present study was designed 1/ to determine the stage in the maturation sequence of bone marrow monocytopoesis in which FXIII appears 2/ to establish if FXIII is retained during differentiation into macrophages 3/ to assess how general is the presence of FXIII subunit a in different types of macrophages. FXIII subunit a was immunomorphologically detected in bone marrow smears, in cytospin preparations of cells from serous cavities (pleural, peritoneal, pericardial and synovial spaces), and paraformaldehyde-fixed paraffin-embedded or frozen sections of different organs where classical types of macrophages have been described earlier (liver, lung, thymus, skin, connective tissue, prostate and developing bone) . Cells containing FXIII subunit a were intensively characterized by immunofluorescent and enzymecytochemical techniques in double and treble labeling systems. Its presence was clearly demonstrated in promonocytes of bone marrow, and in all probability, it is present in monoblasts, as well. FXIII was also found in macrophages from different serous cavities and in embryonic osteoclasts. Cells containing FXIII subunit a of connective tissue were found to be tissue histiocytes, and not fibroblasts as previously thought. Kupffer cells of the liver and Langerhans cells of the epidermis were negative supporting theories that these cells are not members of monocyte-derived macrophage cell population. Immunomorphological detection of FXIII subunit a seems to be a useful marker for labeling the continuum of monocyte/macrophage cell line from the earliest ftrais in the bone marrow to the mature forms of macrophages and might be a valuable tool in the cytological diagnosis of malignant disorders of this cell line.