The efficacy of sodium fluoride therapy for osteoporosis remains controversial. Evidence from clinical studies and from animals receiving fluoride has suggested that fluoride might act on bone to increase osteoblast numbers and matrix synthesis. In order to examine the hypothesis that fluoride has a direct mitogenic or anabolic action on the osteoblast, we tested the effect of fluoride on first passage human osteoblastic bone cells grown from collagenase-treated trabecular bone fragments. Under a variety of culture conditions, including both medium supplementation with serum and with a chemically defined medium, fluoride in doses ranging from 10(-6) to 10(-3) M did not alter cell proliferation as measured either by thymidine incorporation or by direct cell counting. Furthermore, exposure to fluoride under conditions of low serum supplementation did not alter either the total protein synthesis of the cells or their biosynthetic profile. These data suggest that fluoride does not act in vitro upon differentiated osteoblastic bone cells derived from adult human patients.