The safety and efficacy of influenza vaccination were studied in 32 healthy volunteers and in 62 patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, degenerative joint disease, and other rheumatic diseases. These individuals, none of whom was acutely ill, were examined at the time of immunization and one week, three weeks, and four months later. Flare-ups of rheumatic disease following immunization were infrequent and usually minor. Seroconversion to A/New Jersey/76 developed in 62% to 87% of all individuals and to A/Victoria/75 in 62% to 69%. Antibody responses to A/New Jersey/76 were significantly lower in young patients taking glucocorticoids compared to those not taking glucocorticoids. The antibody responses to A/New Jersey/76 and A/Victoria/75 in patients with SLE were not different from normal responses. Administration of these vaccines was safe in these patients with stable disease and induced antibody responses in most individuals.