Hepatitis B virus (HBV)-related polyarteritis nodosa (PAN) is a rare disease whose frequency has been decreasing over the past 10 years. We evaluated 41 patients with HBV-related PAN to determine the circumstances leading to infection, the clinical features of vasculitis, the prognostic factors, and the response to therapy. Most patients were first treated briefly with corticosteroids, and all were included in 2 nonrandomized prospective therapeutic trials of an antiviral agent (35 patients with vidarabine, 6 patients with interferon-alpha 2b) and plasma exchanges. The mean duration of follow-up was 69.6 +/- 44.8 months. At the end of the study, 21 (51.2%) patients had seroconverted to anti-HBeAb and 10 (24.4%) also had seroconverted to anti-HBsAb. In all, 23 (56%) patients no longer expressed serologic evidence of HBV replication. All 33 (80.5%) patients still alive at the end of follow-up recovered from PAN. Nineteen also recovered from HBV infection and were considered to be cured; 13 patients had persistent HBV infection and were considered to be in clinical recovery; and 1 patient was in remission, maintained with steroid therapy. Eight patients died during the study period; 3 deaths were directly attributable to PAN. HBV-related PAN is an acute disease, occurring shortly after infection and sharing the characteristics of classic PAN. It is not an antineutrophil cytoplasm antibodies (ANCA)-mediated vasculitis. The outcome was good for patients treated with short-term steroid therapy, antiviral agents, and plasma exchanges. We propose this protocol as the first treatment for HBV-related PAN, because it surpasses the conventional treatment with corticosteroids and cyclophosphamide, which facilitates viral replication and the development of chronic HBV infection.