Recent studies have suggested that sodium fluoride therapy may be an effective treatment for vertebral osteoporosis. Unfortunately, the high frequency of side effects may limit the use of this treatment modality. This report documents the repeated exacerbation of rheumatoid arthritis on three occasions after the initiation of sodium fluoride therapy. This apparent complication of sodium fluoride treatment may be mediated by stimulation of leukocyte production of reactive oxygen species and other mediators of the acute inflammatory response. We suggest that sodium fluoride should be used cautiously in patients with rheumatoid arthritis.