Objectives. Neutrophils when activated generate a respiratory burst which has been implicated in the pathogenesis of primary systemic vasculitis. Neutrophils front patients with vasculitis have a greater respiratory burst than normal healthy donors. The aim of this study Was to assess the effects of antioxidant treatment (vitamins E and C) on the generation of a respiratory burst from neutrophils isolated from patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Methods. Neutrophils were isolated from patients with systemic vasculitis and healthy donors. Spontaneous superoxide generation was measured by the reduction of ferricytochrome c. The patients were treated with antioxidants. vitamins E and C. and spontaneous Superoxide,generation, vitamin C and total antioxidant capacity were measured before and after treatment. Results. The treatment of the patients with antioxidants resulted in a reduction in spontaneous superoxide generation (pre-treatment 8.41 +/- 0.7 nmol 10(6) cells post-treatment 5.64 +/- 0.6 nmol 10(6) cells: P <0.05). There was no significant difference in the superoxide, generation from normal controls who did not receive treatment, measured prior to commencement of the study and 10 days later (first reading 4.81 +/- 0.5 nmol 10(6) cells: second reading 5.32 +/- 0.4 nmol 10(6) cells P > 0.05). Total antioxidant capacity increased significantly following treatment with vitamins C and E (555.4 +/- 142 vs 668.6 +/- 186 mumol 1 trolox equivalent; P = 0.01) as did vitamin C concentrations (56.5 +/- 27 vs 137.7 +/- 64 mumol 1: P = 0.002). Conclusions. In this preliminary study,. the treatment of patients with antioxidants, vitamins E and C. reduced neutrophil generation of superoxide and Suggests that antioxidants may hake an important role as adjuvant therapy. The evidence presented should form the basis of a larger randomized placebo-controlled trial of vitamins E and C as adjuvant therapy in patients with ANCA-associated systemic vasculitis.