Heavy metals have been postulated to cause significant nitrification inhibition. Using biomass from a well-controlled continuously operated lab-scale nitrifying bioreactor, the effect of nickel and cadmium on ammonium and nitrite oxidation was quantified. The extent of inhibition was calculated from the kinetics of ammonium oxidation and nitrite oxidation, inferred from maximum specific oxygen uptake rates (SOUR) measured in batch respirometric assays. Nickel and cadmium inhibited ammonium oxidation but not nitrite oxidation up to total analytical concentrations of approximately 1.0 mM. Metal fractions (total and free ion) were correlated with the extent of ammonium oxidation inhibition in the presence of various metal complexing agents (EDTA, NTA, citrate, SO4(2-)). Inhibition was not a function of the total analytical metal concentration but strongly correlated with free cation concentration, [Ni2+] or [Cd2+]. This relationship could be described by either an empirical noncompetitive inhibition model for [Ni2+] or a linear model in the case of [Cd2+]. Furthermore, the free Ni2+ or Cd2+ concentrations could be modulated by the addition of a strong chelating agent (e.g., EDTA), resulting in reduced deleterious effects. However, at elevated doses, EDTA itself impaired nitrification. In sum, predictions and mandatory strategies of nitrification inhibition by heavy metals should be based on free cation concentrations and not on total metal concentrations.