OBJECTIVE To address the issues of immunogenicity and local and systemic reactions to vaccination with influenza vaccine in patients with rheumatoid arthritis (RA). METHODS One hundred and twenty-six patients with RA were stratified into 3 groups: (1) those with a history of vaccination with influenza vaccine within 24 months who were receiving usual therapy for RA, (2) those receiving usual therapy for RA but without prior vaccine, and (3) those receiving immunosuppressive medication or prednisone > or = 7.5 mg/day, irrespective of their prior immunization status. Within each group, patients were randomized to receive vaccine or placebo. A group of age matched, healthy controls were also vaccinated. RESULTS During a one month followup period, adverse reactions occurred with equal frequency among patients with RA and healthy controls. Similar significant increases in titers to the vaccine were seen in all groups of patients with arthritis and in the controls. CONCLUSIONS The potential increase in susceptibility to influenza and death from respiratory illness in patients with RA and the demonstrated safety and immunogenicity of influenza vaccine should require the inclusion of patients with RA in standard immunization programs.