Fluoride therapy has been credited with remarkable success in reducing the incidence of tooth decay. Medium to high doses of fluoride have been used in the treatment of osteoporosis. The precise mode of action of fluoride on teeth and bone has yet to be elucidated. It is often assumed that, except in rare circumstances, plasma and extracellular fluid levels of ionic fluoride will not reach concentrations capable of interfering with the normal functioning of human cells. However, fluoride accumulates in skeletal tissues and may be concentrated in the surface layers of the lacunae and canaliculae of bone. Such a hypothetical mechanism may help to clarify the pathogenesis of the osseous lesions in skeletal fluorosis. This hypothesis should be tested in view of recent findings which show that sodium fluoride has a genotoxic effect on embryonic cell culture lines, and can interfere with DNA synthesis in human oral keratinocytes.