Titanium has been used successfully for decades in orthopaedic and dental implants, but the mechanism mediating its biocompatible properties has not been elucidated. The authors investigated the possible role of titanium in modulating reactive oxygen mediators typically produced during the inflammatory response. Peroxynitrite is a highly reactive and unstable inflammatory mediator produced in vivo. This study found a 200% increase in the rate of degradation of peroxynitrite in the presence of titanium. To measure peroxynitrite reactivity, the nitration of 4-hydroxyphenylacetic acid by the peroxynitrite donor 3-morpholinosydnonimine was used. At a pH of 7.4, passivated titanium surfaces led to a 58% decrease of nitration of 4-hydroxyphenylacetic acid by peroxynitrite compared with controls in the absence of proteins. Surface treatments were found to influence the ability of titanium to inhibit peroxynitrite reactivity. Unpassivated titanium surfaces resulted in only a 10% decrease of nitrated 4-hydroxyphenylacetic acid, whereas titanium treated with hydrogen peroxide resulted in a 70% decrease. Decreases in nitration of 4-hydroxyphenylacetic acid also were seen with titanium in the presence of fibrinogen, 10% fetal calf serum, and sodium bicarbonate buffer. These results suggest that titanium is capable of enhancing the breakdown of the inflammatory mediator peroxynitrite and may account for the biocompatible properties of the material.