One of the major effects of fluoride on oral bacteria is a reduction in acid tolerance, and presumably also in cariogenicity. The reduction appears to involve transport of protons across the cell membrane by the weak acid HF to dissipate the pH gradient, and also direct inhibition of the F1F0, proton-translocating ATPases of the organisms, especially for Streptococcus mutans. This direct inhibition by fluoride was found to be dependent on aluminum. The dependence on aluminum was indicated by the protection against fluoride inhibition afforded by the Al-chelator deferoxamine and by loss of protection after addition of umolar levels of Al3+, which were not inhibitory for the enzyme in the absence of fluoride. The F1 form of the enzyme dissociated from the cell membrane previously had been found to be resistant to fluoride in comparison with the F1F0 membrane-associated form. However, this difference appeared to depend on less aluminum in the F1 preparation in that the sensitivity of the F1 enzyme to fluoride could be increased by addition of umolar levels of Al3+. The effects of Al on fluoride inhibition were apparent when enzyme activity was assayed in terms of phosphate release from ATP or with an ATP-regenerating system containing phosphoenolpyruvate, pyruvate kinase, NADH and lactic dehydrogenase. Also, Be2+ but not other metal cations, e.g. Co2+, Fe2+, Fe3+, Mn2, Sn2+, and Zn2+, served to sensitize the enzyme to fluoride inhibition. The differences in sensitivities of enzymes isolated from various oral bacteria found previously appeared also to be related to differences in levels of Al.(ABSTRACT TRUNCATED AT 250 WORDS)