Anti-neutrophil cytoplasmic antibodies (ANCA) are a group of auto-antibodies directed against components of neutrophil granules and monocyte lysosomes. Since the first description of ANCA by Davies et al in 1982 in patients with segmental necrotizing glomerulonephritis, ANCA have been demonstrated in a number of primary vasculitic syndromes [1]. In 1985, van der Woude et al reported on ANCA as a specific and sensitive marker for active Wegener’s granulomatosis [2]. ANCA were later shown to be present in Churg-Strauss syndrome [3, 4], microscopic polyangiitis [5], and pauci-immune necrotizing crescentic glomerulonephritis (NCGN)[6, 7]. In most cases of systemic vasculitis, the primary target antigens for ANCA are proteinase 3 (Pr3), a serine proteinase, and myeloperoxidase (MPO), an enzyme involved in the production of reactive oxygen intermediates [6, 8–10]. Both enzymes are present in secretory granules of neutrophils and monocytes. Although anti-Pr3 and anti-MPO are found across the spectrum of ANCA-associated vasculitides, it is now well established that anti-Pr3 is a sensitive marker for Wegener’s granulomatosus whereas anti-MPO is predominantly found in microscopic polyangiitis, pauci-immune NCGN, and Churg-Strauss syndrome [11]. Although not uniformly accepted, changes in titers of ANCA seem to reffect changes in disease activity [12–16]. Besides being a helpful diagnostic tool, their strong association with primary vasculitic syndromes suggests an important role for ANCA in the pathophysiology of the associated diseases. Experimental evidence for the pathogenic potential of ANCA has been derived mainly from in vitro studies. These studies have provided a wealth of information on the interaction of ANCA with their target antigens and their capacity to activate neutrophils and/or monocytes. The relevance of these in vitro phenomena for the pathophysiology of ANCA-associated systemic vasculitides is, however, far from clear. Experimental research on ANCA-associated vasculitis clearly needs satisfactory animal models [17]. In recent years, several animal studies have been reported on ANCA and vasculitis using various experimental approaches. The present article reviews these studies and evaluates their implications for the pathogenesis of ANCA-associated systemic vasculitis. First, a brief overview will be given on experimental in vitro data substantiating a pathophysiological role for ANCA.