The work described considers the effects on calcified tissues of those concentrations of fluoride which are not overtly cyto-toxic, i.e., in the general region of up to 1-2 mumol/L. Plasma fluoride concentrations or those of the cellular environment are considered rather than dietary levels. The effect of fluoride ion on specific stages of tooth and bone development is discussed. Little effect has been observed on the modulation of gene expression as far as odontogenesis is concerned, although there is evidence that fluoride could be osteogenic in both embryonic and adult tissues. Expression of extracellular matrix protein genes seems not to be impaired, but subtle changes detected in the enamel matrix could be due to selective alterations in amino-acid uptake or interference with subsequent protein processing. This could also be due to an extension of the secretory period without concomitant changes in post-secretory matrix processing. Removal of matrix is apparently impaired, with concomitant incomplete maturation. While existing mineral phases can be affected, it is more likely that matrix and or mineral-matrix interaction is the site of action. Explant studies suggest that the effect may be reversible. Inhibition of proteolysis during enamel maturation may account for the reported inhibition of enamel crystal growth. This is supported by the finding that the normally incomplete maturation of porcine enamel is associated with a somewhat greater residual protein content. The use of animal models in the investigation of enamel dysplasia (fluoride-induced or otherwise) should therefore be viewed with caution.