OBJECTIVE: To study the nature of multinucleated and mononuclear cells from peripheral giant cell granuloma (PGCG).MATERIALS AND METHODS: Formalin‐fixed, paraffin‐embedded sections of 40 cases of PGCG were immunohistochemically stained for vimentin, alpha I‐antichymotrypsin, CD68, S‐100 protein, lysozyme. leucocyte common antigen (LCA), factor VIII‐retated antigen and muscle cell actin. Six cases of PGCG were also studied by transmission etectron microscopy.RESULTS: Vimentin, alpha I‐antichymotrypsin and CD68 were expressed in both the mononuclear and multinucleated giant cells. Dendritic mononuclear cells, positive for 5–100 protein, were noted in 67.5% of the lesions, whereas lysozyme and leucocyte common antigen were detected in occasional mononuclear cells. Ultrastructural examination showed mononuclear cells with signs of phagocytosis and sometimes interdigitations with similar cells. Others presented non‐specific characteristics and the third type exhibited cytoplasmic processes and occasional Birbeck granules. Some multi‐nucleated giant cells showed oval nuclei, abundant mitochondria and granular endoplasmic reticulum whereas others presented with irregular nuclei and a great number of cytoplasmic vacuoles.CONCLUSIONS: lmmunohistochemical and ultrastructural results suggest that PGCGs of the jaws are composed mainly of cells of the mononuclear phagocyte system and that Langerhans cells are present in two thir