Wegener's granulomatosis (WG) is an inflammatory disorder characterized by granulomatous inflammation and vasculitis, and is strongly associated with antineutrophil cytoplasmic antibodies (ANCA). ANCA in patients with WG are directed against proteinase 3 (Pr3) in most of the cases. In vitro, upon neutrophil priming, ANCA antigens are expressed on the cell surface, thereby becoming available for interaction with ANCA. Subsequently, these neutrophils become activated. Since ANCA can only interact with leucocytes when the ANCA antigens are present on the cell surface, we questioned whether Pr3 is already expressed on the membranes of circulating granulocytes and monocytes of patients with WG, and whether Pr3 expression is related to disease activity, so explaining the systemic nature and severity of the disease. The expression of Pr3, and other ANCA antigens, i.e. myeloperoxidase (MPO) and human leucocyte elastase (HLE), was analysed on circulating granulocytes and monocytes by flow cytometry, using a non-activating whole-blood method. Disease activity was quantitated using the Birmingham Vasculitis Activity Score (BVAS). Seventeen patients with active WG and anti-Pr3 antibodies were included in this study. Nine of these patients were also analysed at the time of remission. Twelve patients with sepsis served as positive controls, and 10 healthy volunteers as negative controls for granulocyte/monocyte activation. Pr3 expression on neutrophils was increased in patients with active WG compared to patients with quiescent disease and healthy controls. On monocytes, no differences in Pr3 expression were found between those groups. Furthermore, the expression of MPO and HLE did not differ between patient groups and healthy controls. Upon follow-up, the expression of Pr3 on neutrophils from patients with active WG decreased when patients went into remission. Pr3 expression on neutrophils correlated with the BVAS score (r = 0.40, P < 0.05). In conclusion, circulating neutrophils from patients with active WG have increased expression of Pr3. In addition, the expression of Pr3 correlates with disease activity, suggesting that the availability of Pr3 for interaction with ANCA plays a central role in the disease process.