ANCA are found in various systemic vasculitis and are supposed to play a role in the pathogenesis of the disease, in co-operation with other factors such as cytokines. A total of 36 ANCA-positive and 10 ANCA-negative serum samples were analysed for the presence of TNF soluble receptors (TNF-sR), which are shed from the surface of activated cells and may act as TNF inhibitors. Of the ANCA-positive samples, 67% had elevated TNF-sR75 and 72% had elevated TNF-sR55 compared to ANCA-negative specimens (mean [S.E.] 18.7 [17.3] vs 3.6 [1.5] and 10.5 [9.7] vs 1.9 [0.7] ng/ml, P < 0.01). Elevation of TNF-sR in patients with ANCA suggests that cytokines and their inhibitors are involved in the pathogenesis of ANCA-associated autoimmune diseases.