Immunolabeling with two new antibodies, Factor XIII a and MAC 387, has been studied in routinely processed biopsy specimens of normal skin, subcutaneous tissues, lymph nodes, and a variety of pathological conditions. These presumptive cell markers of the monocyte-macrophage lineage appear to label totally different and possibly mutually exclusive subsets of cells. In normal skin, Factor XIII a labeled fixed dermal connective tissue cells, emphasizing their dendritic morphological appearance. Factor XIII a expression in fibroproliferative conditions and spindle cell tumors varied: in particular, scars, keloids, and dermatofibrosarcomas do not label, whereas histiocytomas, fibrous papule of the nose, and atypical fibroxanthomas were well labeled. In inflammatory conditions, increased numbers of Factor XIII a cells were found, but most macrophages and epithelioid and multinucleate cells did not label. In contrast, normal dermal connective tissue cells did not label with MAC 387, nor did the constituent cells of various fibroproliferative disorders. In inflammatory conditions, variable numbers of MAC 387-positive cells were observed, corresponding to histiocytes and macrophages, but labeling of epithelioid cells and multinucleate foreign body giant cells was variable. Histiocytosis X cells do not express either label. The theoretical and practical implications of these results are explored