In adult human bone, fluoride uptake is accompanied by an increase in apatite crystal size. This increase, however, is not isotropic but is restricted primarily to growth in width and/or thickness, with no measurable change in length. In the present study, seeded growth experiments were conducted in vitro to determine whether this anisotropic effect is physicochemical in origin, i.e., a direct result of F- selectively enhancing lateral crystal growth, or is an indirect consequence of F--induced alterations in cellular function and matrix development. The growth reactions were maintained at 37 degrees C under physiologic-like solution conditions (1.33 mmol/liter Ca2+, 1.0 mmol/liter total phosphate, 0 or 26 mmol/liter carbonate, 270 mmol/kg osmolality, pH 7.4) using constant-composition methods. When new accretions accumulated to three times the initial seed mass, the solids were collected and net crystal growth was assessed by X-ray diffraction Line broadening analysis. The X-ray results revealed that the carbonate constituent in our physiologic-like solutions promoted the proliferation of new crystals at the expense of further growth of the seed apatite. Solution F- concentrations of similar to 2 mu mol/liter partially offset the repressive effect that carbonate had on primary crystal growth. Moreover, F- stimulated seed crystal growth in the same anisotropic manner as had been observed for adult human bone apatite, a finding that suggests that the latter growth in vivo was the consequence, in part, of direct F--mineral interactions.