Fluoride (F-) inhibition of peroxidase activity in whole saliva and of recombinant human myeloperoxidase was investigated using thiocyanate (SCN-) and chloride (Cl-) as substrates. At pH 5.5, SCN(-)-linked activity in whole saliva reduced to < 40% of its initial value at F- concentration of 20 mM, while Cl- linked activity was maintained at 90% of its initial value for the same F-concentration. Based on this Cl(-)-linked activity, the contribution of natural MP to the SCN(-)-linked activity in whole saliva can be calculated. This shows a total inhibition of SCN- dependent activity of salivary peroxidase (SP) for F-concentrations > 10 mM. At a 20 mM F-concentration, recombinant MP activity reduced to 66% of its initial value with SCN-, against 88% for Cl- as substrate. This inhibition of the SCN- linked SP activity is enhanced at acid pH for a F-concentration of 20 mM: 26% residual activity at pH 5 for whole saliva + SCN-against 93% for whole saliva + Cl-; 61% for recombinant MP + SCN- and 88% for MP + Cl-. Calculated activities for SP alone showed a total inhibition at pH 5, while the inhibition was absent at pH 6.5. F-inhibition in whole saliva could also be suppressed by the addition of hydrogen peroxide.