The response of patients with systemic lupus erythematosus and normal subjects to systemic immunization and boosting with influenza A vaccines was studied. Symptoms after vaccination were somewhat more frequent in the patients than in the normal subjects; however, all symptoms were minor and no major flare of illness occurred. No significant induction or increase of pre-existing autoantibodies among the patients was detected after vaccination. The immunogenecity of the vaccinations, as assessed by antibody titers, was similar in the patient and control groups. No correlation between serologic response to influenzal antigens and HLA was found. Thus, in this group of patients with systemic lupus erythematosus, who were either in remission or had mild-to-moderate disease activity, killed influenzal vaccination caused no apparent worsening of disease activity.