Heme-linked ionizations of the acidic and basic isoenzymes of ferrous horseradish peroxidase influence both the Fe-histidine stretching mode and the oxidation-state marker line. First, Raman difference spectroscopy of horseradish peroxidase confirms earlier work showing that v(Fe-His) undergoes a transition in frequency with a pK that is characteristic of the enzyme's functional properties. The Fe-histidine mode shifts by about 2.5-3.0 cm-1 for horseradish peroxidase C and by about 6 cm-1 for the acidic isoenzyme. Further, we find that the oxidation-state marker line v4 also exhibits a transition with the same pK. For horseradish peroxidase C the shift in v4 is 0.4 cm-1 and the pK is 7.1 +/- .5, in good agreement with the pK found by other techniques. Shifts in these two Raman lines are correlated for the pK 7.1 transition and attain their highest frequency at low pH. The correlation is in marked contrast with R/T shifts in hemoglobins for which delta v(Fe-His) and delta v4 are also linearly related but shift in opposite directions. The shift in v4 suggests a mechanism for pH control of catalytic function based on ring pi-charge density effects on the energy of charge-depleted high oxidation-state intermediates. A second transition in v4 (delta v4 = 2.6 cm-1) with a pK of 10.0 is interpreted in terms of a change in ligation and spin state.