Growth and environmental conditions affected the fluoride (F) sensitivity of acid production by Streptococcus sanguis NCTC 7865. Cells grown glucose-limited in a chemostat were generally more sensitive than those harvested from cultures in which there was an excess of glucose (amino acid-limited). There was no consistent relationship between the growth rate of cells and their F sensitivity. Slower-growing cells (mean generation time = 14 hr) were more sensitive than those growing quickly when glucose was the limiting nutrient, whereas the faster growing cells from the glucose-excess culture were most susceptible. The pH of the environment markedly affected the F sensitivity of cells: 2 mM F- was sufficient to abolish acid production by cells incubated at pH 5.0, whereas 24 mM F- did not totally inhibit glycolysis at pH 7.0 or 8.0. Regardless of pH and growth conditions, the cationic composition of the environment had the most pronounced effect on acid production and fluoride sensitivity. Cells washed and re-suspended in KCl were more acidogenic and more sensitive to F than the same cells treated with saline. At pH 7.0 and 8.0, saline-washed cells were comparatively unaffected by F, while glycolysis by the same cells at the same pH but washed in KCl could be inhibited by up to 80%. These results suggested that F inhibition could not be explained merely on the basis of HF uptake at low pH values. Since it has been shown previously that the activity of the energized membrane is maintained by K+ and dissipated in the presence of Na+, it was proposed that proton motive force (pmf) might be involved in the uptake of F-.