Antineutrophil cytoplasmic autoantibodies (ANCA) react with proteins found in the granules of neutrophils and the peroxidase‐positive lysosomes of monocytes, including myeloperoxidase (MPO), proteinase 3 (PR‐3), and elastase. ANGA‐associated diseases, such as Wegener's granulomatosis and polyarteritis nodosa, are characterized by necrotizing vascular inflammation. The inflammatory lesions typically contain both neutrophils and mononuclear phagocytes, with the latter sometimes predominating, for example, in the granulomatous lesions of Wegener's granulomatosis. We investigated the presence of the ANCA target antigens PR3, MPO, and elastase in mononuclear phagocyte cytoplasm during the course of differentiation in vitro and in alveolar and peritoneal macrophages. We observed that ANCA antigens were down‐regulated during mononuclear phagocyte differentiation, with the loss corresponding to that of peroxidase‐positive granules. This suggests that ANCA can directly interact only with monocytes and early exudative macrophages and not with mature macrophages.