OBJECTIVE: to assess the safety and efficacy of influenza vaccination in patients with systemic lupus erythematosus (SLE), and to evaluate the influence of immunosuppressive drugs on the immune response. METHODS: SLE patients (n=56) and healthy controls (n=18) were studied. All patients had quiescent disease (SLE disease activity index<or=5). Four patient groups were defined on the basis of their drug use: (1) no drug treatment; (2) hydroxychloroquine treatment; (3) azathioprine treatment; (4) prednisone treatment. Participants received trivalent influenza subunit vaccine during October/November 2003. Disease activity scores and side effects were recorded. Antibody titres against influenza virus were measured before and 30 days after vaccination using the haemagglutination inhibition assay. RESULTS: Influenza vaccination did not result in changes in disease activity and was well tolerated. SLE patients had fewer seroconversions or fourfold titre rises for A/H1N1 (p<0.001) and A/H3N2 (p<0.001) than healthy controls, while for B/Hong Kong the difference was of borderline significance (p=0.051). With regard to immunosuppressive treatment, fewer SLE patients using azathioprine developed fourfold titre rises against A/H3N2 (p=0.041), and fewer achieved titres of >or=40 against A/H3N2 (p=0.030) compared with the other patient groups. CONCLUSIONS: Influenza vaccination in SLE patients with quiescent disease is safe but is less effective than in controls. Use of azathioprine was associated with a trend to decreased vaccination efficacy.