Synthetic nitroxide antioxidants attenuate oxidative damage in various experimental models. Their protective effect reportedly depends on ring size and ring substituents and is greater for nitroxides having lower oxidation potential. The present study focuses on the kinetics and mechanisms of the reactions of piperidine, pyrrolidine and oxazolidine nitroxides with HO2 center dot/O-2(center dot-), (NO2)-N-center dot and CO3 center dot- radicals, which are key intermediates in many inflammatory and degenerative diseases. It is demonstrated that nitroxides are the most efficient scavengers of (NO2)-N-center dot at physiological pH (k = (3-9) x 10(8) M-1 s(-1)) and among the most effective metal-independent scavengers Of CO3 center dot- radicals (k = (2 - 6) x 10(8) M-1 s(-1)). Their reactivity toward HO2 center dot, though not toward center dot NO2 and CO3 center dot-, depends on the nature of the ring side-chain and particularly on the ring-size. All nitroxide derivatives react slowly with O-2(center dot-) and are relatively inefficient SOD mimics at physiological pH. Even piperidine nitroxides, having the highest SOD-like activity, demonstrate a catalytic activity of about 1000-fold lower than that of native SOD at pH 7.4. The present results do not indicate any correlation between the kinetics of HO2 center dot/O-2(center dot-), (NO2)-N-center dot, and CO3 center dot- removal by nitroxides and their protective activity against biological oxidative stress and emphasize the importance of target-oriented nitroxides, i.e., interaction between the biological target and specific nitroxides.