Proteinase 3 was identified as the target antigen of anticytoplasmic antibodies (ACPA/c-ANCA) in Wegener's granulomatosis (WG). Using the murine monoclonal antibody (MAb) WGM2, the authors localized proteinase 3 on normal and pathologic tissue and in various human cell lines. Proteinase 3 was found in all granulocytes, mast cells, and a subset of monocytes (2-10% of peripheral blood monocytes). No crossreactivity of the MAb with other cells or tissue components was observed. Comparing various vasculitic and granulomatous tissues, WG granulomas contained more granulocytes. In tissue of WG, no crossreactivity of the MAb with tissue components such as blood vessel wall or endothelium was seen. The monocytic line THP-1 and the promyelocytic line HL 60 contained proteinase 3. Since proteinase 3 was only found in neutrophil granulocytes, mast cells, and a subset of monocytes, the presented data provide further evidence that granulocytes play a central role in the pathogenesis of WG.