Nitrogen monoxide (nitric oxide) generated endogenously has a variety of different properties. Among others it regulates blood pressure and transmission of nerve impulses, and has been shown to exert specific toxic effects, but also, paradoxically, to protect against various toxic substances. Recent studies suggest that NO^· can serve as an antioxidant of the highly oxidizing ferryl myoglobin (MbFe^IV=O), which has been proposed to be at least in part responsible for the oxidative damage caused by the reperfusion of ischemic tissues. In the present work we have determined the rate constant for the reaction between MbFe^IV=O and NO^· [(17.9±0.5)×10⁶ M^–1 s^–1 at pH 7.5 and 20 °C] and we have shown that this reaction proceeds via the intermediate nitrito-metmyoglobin complex MbFe^IIIONO. Our results imply that this reaction is very likely to take place in vivo and might indeed represent a detoxifying pathway for both MbFe^IV=O as well as NO^·. Moreover, we have found that the rate of reaction of MbFe^IV=O with nitrite is significantly lower (16±1 M^–1 s^–1 at pH 7.5 and 20 °C). Thus, this reaction probably plays a role only when NO^· has been consumed completely and large concentrations of nitrite are still present. In contrast to the protecting role of NO^·, the reaction with nitrite generates nitrogen dioxide which can contribute to tyrosine nitration. Indeed, we have demonstrated that nitrite can nitrate added tyrosine in the presence of iron(III) myoglobin and hydrogen peroxide.